SARS-CoV-2 Variants, Current Vaccines and Therapeutic Implications for COVID-19
Abstract
:1. Introduction
2. Predominant Variants of SARS-CoV-2 (Figure 1)
2.1. Alpha (B.1.1.7 Lineage) Variant
2.2. Beta (B.1.351 Lineage) Variant
2.3. Gamma (P.1 Lineage) Variant
2.4. Delta (B.1.617.2 Lineage) Variant
2.5. Omicron (B.1.1.529 Lineage) Variant
2.6. Other Variants
2.6.1. Lambda Variant
2.6.2. Mu Variant
2.6.3. Kappa Variant
3. Current Vaccine
3.1. Pfizer/BioNTech mRNA Vaccine
3.2. Moderna mRNA-1273 Vaccine
3.3. AZD1222 Vaccine
3.4. CoronaVac Vaccine
3.5. DNA Vaccine
3.6. NVX CoV-2373 Vaccine
4. Potential Molecular Therapeutic Target (Table 3)
4.1. S Protein
Pharmacological Target | Role of Target in Viral Infection | Therapeutic Strategy | Drug Candidate |
---|---|---|---|
S protein | Binds to ACE2, mediates virus-host fusion | block | Monoclonal antibodies (such as bamlanimab, etesevimab, etc.) or vaccines |
ACE2 | Binds to S protein, mediates virus-host fusion; Mediates Ang-II-induced toxicity during COVID-19 | block | infusion of transgenic human recombinant soluble ACE2 (hrsACE2) or circulating extracellular vesicle ACE2 (evACE2) |
IL-6 | Causes tissue damage and promotes a flare-up of inflammation | inhibit | tocilizumab |
IL-1 | inhibit | anakinra | |
TNF-α | inhibit | Adalimumab; N-acetylcysteine; tramadol | |
MPro | Facilitates the processing of viral proteins | inhibit | nirmatrelvir |
TMPRSS2 | Responsible for cleaving the S protein and promoting the binding of ACE2 to the S protein | inhibit | Camostat; nafamostat |
4.2. ACE2
4.3. Inflammatory Cytokine
4.3.1. Anti IL-6
4.3.2. Anti IL-1
4.3.3. Anti TNF-α
4.4. MPro
4.5. TMPRSS2
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Hu, B.; Guo, H.; Zhou, P.; Shi, Z.L. Characteristics of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol. 2021, 19, 141–154. [Google Scholar] [CrossRef] [PubMed]
- Jiang, Y.; Wu, Q.; Song, P.; You, C. The Variation of SARS-CoV-2 and Advanced Research on Current Vaccines. Front. Med. 2021, 8, 806641. [Google Scholar] [CrossRef]
- Chan, J.F.; Kok, K.H.; Zhu, Z.; Chu, H.; To, K.K.; Yuan, S.; Yuen, K.Y. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg. Microbes Infect 2020, 9, 221–236. [Google Scholar]
- Watanabe, Y.; Berndsen, Z.T.; Raghwani, J.; Seabright, G.E.; Allen, J.D.; Pybus, O.G.; McLellan, J.S.; Wilson, I.A.; Bowden, T.A.; Ward, A.B.; et al. Vulnerabilities in coronavirus glycan shields despite extensive glycosylation. Nat. Commun. 2020, 11, 2688. [Google Scholar] [CrossRef] [PubMed]
- Delmas, B.; Laude, H. Assembly of coronavirus spike protein into trimers and its role in epitope expression. J. Virol. 1990, 64, 5367–5375. [Google Scholar] [CrossRef] [PubMed]
- Volz, E.; Mishra, S.; Chand, M.; Barrett, J.C.; Johnson, R.; Geidelberg, L.; Hinsley, W.R.; Laydon, D.J.; Dabrera, G.; O’Toole, A.; et al. Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature 2021, 593, 266–269. [Google Scholar] [CrossRef]
- Mwenda, M.; Saasa, N.; Sinyange, N.; Busby, G.; Chipimo, P.J.; Hendry, J.; Kapona, O.; Yingst, S.; Hines, J.Z.; Minchella, P.; et al. Detection of B.1.351 SARS-CoV-2 Variant Strain—Zambia, December 2020. MMWR Morb. Mortal. Wkly. Rep. 2021, 70, 280–282. [Google Scholar] [PubMed]
- Hirotsu, Y.; Omata, M. Discovery of a SARS-CoV-2 variant from the P.1 lineage harboring K417T/E484K/N501Y mutations in Kofu, Japan. J. Infect. 2021, 82, 276–316. [Google Scholar] [CrossRef]
- Padilla-Rojas, C.; Jimenez-Vasquez, V.; Hurtado, V.; Mestanza, O.; Molina, I.S.; Barcena, L.; Morales Ruiz, S.; Acedo, S.; Lizarraga, W.; Bailon, H. Genomic analysis reveals a rapid spread and predominance of lambda (C.37) SARS-COV-2 lineage in Peru despite circulation of variants of concern. J. Med. Virol. 2021, 93, 6845–6849. [Google Scholar] [CrossRef]
- Carrazco-Montalvo, A.; Bruno, A.; de Mora, D.; Olmedo, M.; Garces, J.; Paez, M.; Regato-Arrata, M.; Gonzalez, M.; Romero, J.; Mestanza, O.; et al. First Report of SARS-CoV-2 Lineage B.1.1.7 (Alpha Variant) in Ecuador, January 2021. Infect. Drug Resist. 2021, 14, 5183–5188. [Google Scholar] [CrossRef]
- Yang, T.J.; Yu, P.Y.; Chang, Y.C.; Liang, K.H.; Tso, H.C.; Ho, M.R.; Chen, W.Y.; Lin, H.T.; Wu, H.C.; Hsu, S.D. Effect of SARS-CoV-2 B.1.1.7 mutations on spike protein structure and function. Nat. Struct. Mol. Biol. 2021, 28, 731–739. [Google Scholar] [PubMed]
- Gobeil, S.M.; Janowska, K.; McDowell, S.; Mansouri, K.; Parks, R.; Stalls, V.; Kopp, M.F.; Manne, K.; Li, D.; Wiehe, K.; et al. Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity. Science 2021, 373, eabi6226. [Google Scholar] [CrossRef] [PubMed]
- Janik, E.; Niemcewicz, M.; Podogrocki, M.; Majsterek, I.; Bijak, M. The Emerging Concern and Interest SARS-CoV-2 Variants. Pathogens 2021, 10, 633. [Google Scholar] [CrossRef] [PubMed]
- Davies, N.G.; Abbott, S.; Barnard, R.C.; Jarvis, C.I.; Kucharski, A.J.; Munday, J.D.; Pearson, C.A.B.; Russell, T.W.; Tully, D.C.; Washburne, A.D.; et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 2021, 372, eabg3055. [Google Scholar] [CrossRef] [PubMed]
- Meng, B.; Kemp, S.A.; Papa, G.; Datir, R.; Ferreira, I.; Marelli, S.; Harvey, W.T.; Lytras, S.; Mohamed, A.; Gallo, G.; et al. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7. Cell Rep. 2021, 35, 109292. [Google Scholar] [CrossRef]
- Liu, Y.; Liu, J.; Plante, K.S.; Plante, J.A.; Xie, X.; Zhang, X.; Ku, Z.; An, Z.; Scharton, D.; Schindewolf, C.; et al. The N501Y spike substitution enhances SARS-CoV-2 infection and transmission. Nature 2022, 602, 294–299. [Google Scholar] [CrossRef] [PubMed]
- Zhu, X.; Mannar, D.; Srivastava, S.S.; Berezuk, A.M.; Demers, J.P.; Saville, J.W.; Leopold, K.; Li, W.; Dimitrov, D.S.; Tuttle, K.S.; et al. Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies. PLoS Biol. 2021, 19, e3001237. [Google Scholar] [CrossRef]
- Quinonez, E.; Vahed, M.; Hashemi Shahraki, A.; Mirsaeidi, M. Structural Analysis of the Novel Variants of SARS-CoV-2 and Forecasting in North America. Viruses 2021, 13, 930. [Google Scholar]
- Graham, C.; Seow, J.; Huettner, I.; Khan, H.; Kouphou, N.; Acors, S.; Winstone, H.; Pickering, S.; Galao, R.P.; Dupont, L.; et al. Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant. Immunity 2021, 54, 1276–1289 e1276. [Google Scholar] [CrossRef]
- Mohammad, A.; Abubaker, J.; Al-Mulla, F. Structural modelling of SARS-CoV-2 alpha variant (B.1.1.7) suggests enhanced furin binding and infectivity. Virus Res. 2021, 303, 198522. [Google Scholar] [CrossRef]
- Grint, D.J.; Wing, K.; Williamson, E.; McDonald, H.I.; Bhaskaran, K.; Evans, D.; Evans, S.J.; Walker, A.J.; Hickman, G.; Nightingale, E.; et al. Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February. Euro Surveill. 2021, 26, 2100256. [Google Scholar] [CrossRef] [PubMed]
- Cetin, M.; Balci, P.O.; Sivgin, H.; Cetin, S.; Ulgen, A.; Dortok Demir, H.; Li, W. Alpha variant (B.1.1.7) of SARS-CoV-2 increases fatality-rate for patients under age of 70 years and hospitalization risk overall. Acta Microbiol. Immunol. Hung. 2021, 68, 153–161. [Google Scholar] [CrossRef] [PubMed]
- Collier, D.A.; De Marco, A.; Ferreira, I.; Meng, B.; Datir, R.P.; Walls, A.C.; Kemp, S.A.; Bassi, J.; Pinto, D.; Silacci-Fregni, C.; et al. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature 2021, 593, 136–141. [Google Scholar] [CrossRef]
- Muik, A.; Wallisch, A.K.; Sanger, B.; Swanson, K.A.; Muhl, J.; Chen, W.; Cai, H.; Maurus, D.; Sarkar, R.; Tureci, O.; et al. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera. Science 2021, 371, 1152–1153. [Google Scholar] [CrossRef]
- Tegally, H.; Wilkinson, E.; Giovanetti, M.; Iranzadeh, A.; Fonseca, V.; Giandhari, J.; Doolabh, D.; Pillay, S.; San, E.J.; Msomi, N.; et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 2021, 592, 438–443. [Google Scholar] [CrossRef] [PubMed]
- Starr, T.N.; Greaney, A.J.; Hilton, S.K.; Ellis, D.; Crawford, K.H.D.; Dingens, A.S.; Navarro, M.J.; Bowen, J.E.; Tortorici, M.A.; Walls, A.C.; et al. Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell 2020, 182, 1295–1310e1220. [Google Scholar] [CrossRef]
- Greaney, A.J.; Loes, A.N.; Crawford, K.H.D.; Starr, T.N.; Malone, K.D.; Chu, H.Y.; Bloom, J.D. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host. Microbe 2021, 29, 463–476 e466. [Google Scholar] [CrossRef]
- Wilton, T.; Bujaki, E.; Klapsa, D.; Majumdar, M.; Zambon, M.; Fritzsche, M.; Mate, R.; Martin, J. Rapid Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between October 2020 and January 2021. mSystems 2021, 6, e0035321. [Google Scholar] [CrossRef]
- Kim, Y.J.; Jang, U.S.; Soh, S.M.; Lee, J.Y.; Lee, H.R. The Impact on Infectivity and Neutralization Efficiency of SARS-CoV-2 Lineage B.1.351 Pseudovirus. Viruses 2021, 13, 633. [Google Scholar] [CrossRef]
- Starr, T.N.; Greaney, A.J.; Addetia, A.; Hannon, W.W.; Choudhary, M.C.; Dingens, A.S.; Li, J.Z.; Bloom, J.D. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 2021, 371, 850–854. [Google Scholar] [CrossRef]
- Wang, P.; Nair, M.S.; Liu, L.; Iketani, S.; Luo, Y.; Guo, Y.; Wang, M.; Yu, J.; Zhang, B.; Kwong, P.D.; et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 2021, 593, 130–135. [Google Scholar] [CrossRef] [PubMed]
- Cele, S.; Gazy, I.; Jackson, L.; Hwa, S.H.; Tegally, H.; Lustig, G.; Giandhari, J.; Pillay, S.; Wilkinson, E.; Naidoo, Y.; et al. Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma. Nature 2021, 593, 142–146. [Google Scholar] [CrossRef] [PubMed]
- Wu, K.; Werner, A.P.; Moliva, J.I.; Koch, M.; Choi, A.; Stewart-Jones, G.B.E.; Bennett, H.; Boyoglu-Barnum, S.; Shi, W.; Graham, B.S.; et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. bioRxiv, 2021; preprint. [Google Scholar]
- Fujino, T.; Nomoto, H.; Kutsuna, S.; Ujiie, M.; Suzuki, T.; Sato, R.; Fujimoto, T.; Kuroda, M.; Wakita, T.; Ohmagari, N. Novel SARS-CoV-2 Variant in Travelers from Brazil to Japan. Emerg. Infect. Dis. 2021, 27, 1243. [Google Scholar] [CrossRef] [PubMed]
- Tao, K.; Tzou, P.L.; Nouhin, J.; Gupta, R.K.; de Oliveira, T.; Kosakovsky Pond, S.L.; Fera, D.; Shafer, R.W. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat. Rev. Genet. 2021, 22, 757–773. [Google Scholar] [CrossRef] [PubMed]
- Choi, J.Y.; Smith, D.M. SARS-CoV-2 Variants of Concern. Yonsei Med. J. 2021, 62, 961–968. [Google Scholar] [CrossRef] [PubMed]
- McCallum, M.; De Marco, A.; Lempp, F.A.; Tortorici, M.A.; Pinto, D.; Walls, A.C.; Beltramello, M.; Chen, A.; Liu, Z.; Zatta, F.; et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell 2021, 184, 2332–2347 e2316. [Google Scholar] [CrossRef]
- Dejnirattisai, W.; Zhou, D.; Supasa, P.; Liu, C.; Mentzer, A.J.; Ginn, H.M.; Zhao, Y.; Duyvesteyn, H.M.E.; Tuekprakhon, A.; Nutalai, R.; et al. Antibody evasion by the P.1 strain of SARS-CoV-2. Cell 2021, 184, 2939–2954e2939. [Google Scholar] [CrossRef]
- Copin, R.; Baum, A.; Wloga, E.; Pascal, K.E.; Giordano, S.; Fulton, B.O.; Zhou, A.; Negron, N.; Lanza, K.; Chan, N.; et al. The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies. Cell 2021, 184, 3949–3961e3911. [Google Scholar] [CrossRef]
- Hoffmann, M.; Arora, P.; Gross, R.; Seidel, A.; Hornich, B.F.; Hahn, A.S.; Kruger, N.; Graichen, L.; Hofmann-Winkler, H.; Kempf, A.; et al. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 2021, 184, 2384–2393 e2312. [Google Scholar] [CrossRef]
- Wang, P.; Casner, R.G.; Nair, M.S.; Wang, M.; Yu, J.; Cerutti, G.; Liu, L.; Kwong, P.D.; Huang, Y.; Shapiro, L.; et al. Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization. Cell Host. Microbe 2021, 29, 747–751e744. [Google Scholar] [CrossRef] [PubMed]
- Faria, N.R.; Mellan, T.A.; Whittaker, C.; Claro, I.M.; Candido, D.D.S.; Mishra, S.; Crispim, M.A.E.; Sales, F.C.S.; Hawryluk, I.; McCrone, J.T.; et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 2021, 372, 815–821. [Google Scholar] [CrossRef] [PubMed]
- Novelli, G.; Colona, V.L.; Pandolfi, P.P. A focus on the spread of the delta variant of SARS-CoV-2 in India. Indian J. Med. Res. 2021, 153, 537–541. [Google Scholar] [CrossRef]
- Liu, C.; Ginn, H.M.; Dejnirattisai, W.; Supasa, P.; Wang, B.; Tuekprakhon, A.; Nutalai, R.; Zhou, D.; Mentzer, A.J.; Zhao, Y.; et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell 2021, 184, 4220–4236 e4213. [Google Scholar] [CrossRef] [PubMed]
- Ferreira, I.; Kemp, S.A.; Datir, R.; Saito, A.; Meng, B.; Rakshit, P.; Takaori-Kondo, A.; Kosugi, Y.; Uriu, K.; Kimura, I.; et al. SARS-CoV-2 B.1.617 Mutations L452R and E484Q Are Not Synergistic for Antibody Evasion. J. Infect. Dis. 2021, 224, 989–994. [Google Scholar] [CrossRef]
- Dhar, M.S.; Marwal, R.; Vs, R.; Ponnusamy, K.; Jolly, B.; Bhoyar, R.C.; Sardana, V.; Naushin, S.; Rophina, M.; Mellan, T.A.; et al. Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India. Science 2021, 374, 995–999. [Google Scholar] [CrossRef]
- Di Giacomo, S.; Mercatelli, D.; Rakhimov, A.; Giorgi, F.M. Preliminary report on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike mutation T478K. J. Med. Virol. 2021, 93, 5638–5643. [Google Scholar] [CrossRef]
- Greaney, A.J.; Starr, T.N.; Gilchuk, P.; Zost, S.J.; Binshtein, E.; Loes, A.N.; Hilton, S.K.; Huddleston, J.; Eguia, R.; Crawford, K.H.D.; et al. Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition. Cell Host. Microbe 2021, 29, 44–57e49. [Google Scholar] [CrossRef]
- Muecksch, F.; Weisblum, Y.; Barnes, C.O.; Schmidt, F.; Schaefer-Babajew, D.; Wang, Z.; Lorenzi, J.C.C.; Flyak, A.I.; DeLaitsch, A.T.; Huey-Tubman, K.E.; et al. Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations. Immunity 2021, 54, 1853–1868e1857. [Google Scholar] [CrossRef]
- Cherian, S.; Potdar, V.; Jadhav, S.; Yadav, P.; Gupta, N.; Das, M.; Rakshit, P.; Singh, S.; Abraham, P.; Panda, S.; et al. SARS-CoV-2 Spike Mutations, L452R, T478K, E484Q and P681R, in the Second Wave of COVID-19 in Maharashtra, India. Microorganisms 2021, 9, 1542. [Google Scholar] [CrossRef]
- Johnson, B.A.; Xie, X.; Kalveram, B.; Lokugamage, K.G.; Muruato, A.; Zou, J.; Zhang, X.; Juelich, T.; Smith, J.K.; Zhang, L.; et al. Furin Cleavage Site Is Key to SARS-CoV-2 Pathogenesis. bioRxiv, 2020; preprint. [Google Scholar]
- Planas, D.; Veyer, D.; Baidaliuk, A.; Staropoli, I.; Guivel-Benhassine, F.; Rajah, M.M.; Planchais, C.; Porrot, F.; Robillard, N.; Puech, J.; et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 2021, 596, 276–280. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Liu, Y.; Xia, H.; Zou, J.; Weaver, S.C.; Swanson, K.A.; Cai, H.; Cutler, M.; Cooper, D.; Muik, A.; et al. BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants. Nature 2021, 596, 273–275. [Google Scholar] [CrossRef] [PubMed]
- Yadav, P.D.; Sapkal, G.N.; Ella, R.; Sahay, R.R.; Nyayanit, D.A.; Patil, D.Y.; Deshpande, G.; Shete, A.M.; Gupta, N.; Mohan, V.K.; et al. Neutralization of Beta and Delta variant with sera of COVID-19 recovered cases and vaccinees of inactivated COVID-19 vaccine BBV152/Covaxin. J. Travel Med. 2021, 28, taab104. [Google Scholar] [CrossRef]
- O’Dowd, A. COVID-19: Cases of delta variant rise by 79%, but rate of growth slows. BMJ 2021, 373, n1596. [Google Scholar] [CrossRef]
- Fowlkes, A.; Gaglani, M.; Groover, K.; Thiese, M.S.; Tyner, H.; Ellingson, K.; Cohorts, H.-R. Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Frontline Workers Before and During B.1.617.2 (Delta) Variant Predominance—Eight U.S. Locations, December 2020–August 2021. MMWR Morb. Mortal. Wkly. Rep. 2021, 70, 1167–1169. [Google Scholar] [CrossRef]
- Del Rio, C.; Malani, P.N.; Omer, S.B. Confronting the Delta Variant of SARS-CoV-2, Summer 2021. JAMA 2021, 326, 1001–1002. [Google Scholar] [CrossRef]
- Graham, F. Daily Briefing: Why the Delta Variant Spreads So Fast; Nature: Berlin/Heidelberg, Germany, 2021. [Google Scholar]
- Wang, Y.; Chen, R.; Hu, F.; Lan, Y.; Yang, Z.; Zhan, C.; Shi, J.; Deng, X.; Jiang, M.; Zhong, S.; et al. Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China. EClinicalMedicine 2021, 40, 101129. [Google Scholar] [CrossRef]
- Sheikh, A.; McMenamin, J.; Taylor, B.; Robertson, C.; Public Health Scotland the EIIC. SARS-CoV-2 Delta VOC in Scotland: Demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021, 397, 2461–2462. [Google Scholar] [CrossRef]
- Kannan, S.R.; Spratt, A.N.; Cohen, A.R.; Naqvi, S.H.; Chand, H.S.; Quinn, T.P.; Lorson, C.L.; Byrareddy, S.N.; Singh, K. Evolutionary analysis of the Delta and Delta Plus variants of the SARS-CoV-2 viruses. J. Autoimmun. 2021, 124, 102715. [Google Scholar] [CrossRef]
- Gao, S.J.; Guo, H.; Luo, G. Omicron variant (B.1.1.529) of SARS-CoV-2, a global urgent public health alert! J. Med. Virol. 2022, 94, 1255–1256. [Google Scholar] [CrossRef] [PubMed]
- Araf, Y.; Akter, F.; Tang, Y.D.; Fatemi, R.; Parvez, M.S.A.; Zheng, C.; Hossain, M.G. Omicron variant of SARS-CoV-2: Genomics, transmissibility, and responses to current COVID-19 vaccines. J. Med. Virol. 2022, 94, 1825–1832. [Google Scholar] [CrossRef] [PubMed]
- Bansal, K.; Kumar, S. Mutational cascade of SARS-CoV-2 leading to evolution and emergence of omicron variant. Virus Res. 2022, 315, 198765. [Google Scholar] [CrossRef]
- Hoffmann, M.; Kruger, N.; Schulz, S.; Cossmann, A.; Rocha, C.; Kempf, A.; Nehlmeier, I.; Graichen, L.; Moldenhauer, A.S.; Winkler, M.S.; et al. The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic. Cell 2022, 185, 447–456 e411. [Google Scholar] [CrossRef] [PubMed]
- Pulliam, J.R.C.; van Schalkwyk, C.; Govender, N.; von Gottberg, A.; Cohen, C.; Groome, M.J.; Dushoff, J.; Mlisana, K.; Moultrie, H. Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa. Science 2022, 376, eabn4947. [Google Scholar] [CrossRef] [PubMed]
- Li, X. Omicron: Call for updated vaccines. J. Med. Virol. 2022, 94, 1261–1263. [Google Scholar] [CrossRef]
- Lu, L.; Mok, B.W.; Chen, L.L.; Chan, J.M.; Tsang, O.T.; Lam, B.H.; Chuang, V.W.; Chu, A.W.; Chan, W.M.; Ip, J.D.; et al. Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients. Clin. Infect. Dis. 2021, 75, e822–e826. [Google Scholar] [CrossRef]
- Tada, T.; Zhou, H.; Samanovic, M.I.; Dcosta, B.M.; Cornelius, A.; Mulligan, M.J.; Landau, N.R. Comparison of Neutralizing Antibody Titers Elicited by mRNA and Adenoviral Vector Vaccine against SARS-CoV-2 Variants. bioRxiv, 2021; preprint. [Google Scholar]
- Messali, S.; Bertelli, A.; Campisi, G.; Zani, A.; Ciccozzi, M.; Caruso, A.; Caccuri, F. A cluster of the new SARS-CoV-2 B.1.621 lineage in Italy and sensitivity of the viral isolate to the BNT162b2 vaccine. J. Med. Virol. 2021, 93, 6468–6470. [Google Scholar] [CrossRef]
- Edara, V.V.; Lai, L.; Sahoo, M.K.; Floyd, K.; Sibai, M.; Solis, D.; Flowers, M.W.; Hussaini, L.; Ciric, C.R.; Bechnack, S.; et al. Infection and vaccine-induced neutralizing antibody responses to the SARS-CoV-2 B.1.617.1 variant. bioRxiv, 2021; preprint. [Google Scholar]
- Pascarella, S.; Ciccozzi, M.; Zella, D.; Bianchi, M.; Benedetti, F.; Benvenuto, D.; Broccolo, F.; Cauda, R.; Caruso, A.; Angeletti, S.; et al. SARS-CoV-2 B.1.617 Indian variants: Are electrostatic potential changes responsible for a higher transmission rate? J. Med. Virol. 2021, 93, 6551–6556. [Google Scholar] [CrossRef] [PubMed]
- Chen, R.E.; Zhang, X.; Case, J.B.; Winkler, E.S.; Liu, Y.; VanBlargan, L.A.; Liu, J.; Errico, J.M.; Xie, X.; Suryadevara, N.; et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 2021, 27, 717–726. [Google Scholar] [CrossRef] [PubMed]
- Tchesnokova, V.; Kulakesara, H.; Larson, L.; Bowers, V.; Rechkina, E.; Kisiela, D.; Sledneva, Y.; Choudhury, D.; Maslova, I.; Deng, K.; et al. Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-COV-2 variants. bioRxiv, 2021; preprint. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Zang, J.; Xu, S.; Zhang, X.; Yuan, S.; Wang, H.; Lavillette, D.; Zhang, C.; Huang, Z. Elicitation of Broadly Neutralizing Antibodies against B.1.1.7, B.1.351, and B.1.617.1 SARS-CoV-2 Variants by Three Prototype Strain-Derived Recombinant Protein Vaccines. Viruses 2021, 13, 1421. [Google Scholar] [CrossRef]
- World Health Organization. Analysis on COVID-19 Vaccine Price Data from Publicly Available Information and as Reported by Countries; World Health Organization: Geneva, Switzerland, 2022.
- Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Perez Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef]
- Xie, X.; Liu, Y.; Liu, J.; Zhang, X.; Zou, J.; Fontes-Garfias, C.R.; Xia, H.; Swanson, K.A.; Cutler, M.; Cooper, D.; et al. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nat. Med. 2021, 27, 620–621. [Google Scholar] [CrossRef]
- Zou, J.; Xie, X.; Fontes-Garfias, C.R.; Swanson, K.A.; Kanevsky, I.; Tompkins, K.; Cutler, M.; Cooper, D.; Dormitzer, P.R.; Shi, P.Y. The effect of SARS-CoV-2 D614G mutation on BNT162b2 vaccine-elicited neutralization. NPJ Vaccines 2021, 6, 44. [Google Scholar] [CrossRef]
- Liu, Y.; Liu, J.; Xia, H.; Zhang, X.; Fontes-Garfias, C.R.; Swanson, K.A.; Cai, H.; Sarkar, R.; Chen, W.; Cutler, M.; et al. Neutralizing Activity of BNT162b2-Elicited Serum. N. Engl. J. Med. 2021, 384, 1466–1468. [Google Scholar] [CrossRef]
- Vasileiou, E.; Simpson, C.R.; Shi, T.; Kerr, S.; Agrawal, U.; Akbari, A.; Bedston, S.; Beggs, J.; Bradley, D.; Chuter, A.; et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: A national prospective cohort study. Lancet 2021, 397, 1646–1657. [Google Scholar] [CrossRef]
- Saciuk, Y.; Kertes, J.; Shamir Stein, N.; Ekka Zohar, A. Effectiveness of a Third Dose of BNT162b2 mRNA Vaccine. J. Infect. Dis. 2022, 225, 30–33. [Google Scholar] [CrossRef]
- Dickerman, B.A.; Madenci, A.L.; Gerlovin, H.; Kurgansky, K.E.; Wise, J.K.; Figueroa Muniz, M.J.; Ferolito, B.R.; Gagnon, D.R.; Gaziano, J.M.; Cho, K.; et al. Comparative Safety of BNT162b2 and mRNA-1273 Vaccines in a Nationwide Cohort of US Veterans. JAMA Intern Med. 2022, 182, 739–746. [Google Scholar] [CrossRef] [PubMed]
- Barda, N.; Dagan, N.; Ben-Shlomo, Y.; Kepten, E.; Waxman, J.; Ohana, R.; Hernan, M.A.; Lipsitch, M.; Kohane, I.; Netzer, D.; et al. Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. N. Engl. J. Med. 2021, 385, 1078–1090. [Google Scholar] [CrossRef] [PubMed]
- Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 2021, 384, 403–416. [Google Scholar] [CrossRef] [PubMed]
- Chemaitelly, H.; Yassine, H.M.; Benslimane, F.M.; Al Khatib, H.A.; Tang, P.; Hasan, M.R.; Malek, J.A.; Coyle, P.; Ayoub, H.H.; Al Kanaani, Z.; et al. mRNA-1273 COVID-19 vaccine effectiveness against the B.1.1.7 and B.1.351 variants and severe COVID-19 disease in Qatar. Nat. Med. 2021, 27, 1614–1621. [Google Scholar] [CrossRef] [PubMed]
- Kandikattu, H.K.; Yadavalli, C.S.; Venkateshaiah, S.U.; Mishra, A. Vaccine efficacy in mutant SARS-CoV-2 variants. Int J. Cell Biol. Physiol. 2021, 4, 1–12. [Google Scholar]
- Nanduri, S.; Pilishvili, T.; Derado, G.; Soe, M.M.; Dollard, P.; Wu, H.; Li, Q.; Bagchi, S.; Dubendris, H.; Link-Gelles, R.; et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant—National Healthcare Safety Network, March 1-August 1, 2021. MMWR Morb. Mortal. Wkly. Rep. 2021, 70, 1163–1166. [Google Scholar]
- Andrews, N.; Stowe, J.; Kirsebom, F.; Toffa, S.; Rickeard, T.; Gallagher, E.; Gower, C.; Kall, M.; Groves, N.; O’Connell, A.M.; et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N. Engl. J. Med. 2022, 386, 1532–1546. [Google Scholar] [CrossRef]
- Accorsi, E.K.; Britton, A.; Fleming-Dutra, K.E.; Smith, Z.R.; Shang, N.; Derado, G.; Miller, J.; Schrag, S.J.; Verani, J.R. Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants. JAMA 2022, 327, 639–651. [Google Scholar] [CrossRef]
- Klein, N.P.; Lewis, N.; Goddard, K.; Fireman, B.; Zerbo, O.; Hanson, K.E.; Donahue, J.G.; Kharbanda, E.O.; Naleway, A.; Nelson, J.C.; et al. Surveillance for Adverse Events After COVID-19 mRNA Vaccination. JAMA 2021, 326, 1390–1399. [Google Scholar] [CrossRef]
- Watanabe, Y.; Mendonca, L.; Allen, E.R.; Howe, A.; Lee, M.; Allen, J.D.; Chawla, H.; Pulido, D.; Donnellan, F.; Davies, H.; et al. Native-like SARS-CoV-2 Spike Glycoprotein Expressed by ChAdOx1 nCoV-19/AZD1222 Vaccine. ACS Cent. Sci. 2021, 7, 594–602. [Google Scholar] [CrossRef]
- Callaway, E.; Mallapaty, S. Latest Results Put Oxford-AstraZeneca COVID Vaccine Back on Track; Nature: Berlin/Heidelberg, Germany, 2021. [Google Scholar]
- Voysey, M.; Clemens, S.A.C.; Madhi, S.A.; Weckx, L.Y.; Folegatti, P.M.; Aley, P.K.; Angus, B.; Baillie, V.L.; Barnabas, S.L.; Bhorat, Q.E.; et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021, 397, 99–111. [Google Scholar] [CrossRef]
- Madhi, S.A.; Baillie, V.; Cutland, C.L.; Voysey, M.; Koen, A.L.; Fairlie, L.; Padayachee, S.D.; Dheda, K.; Barnabas, S.L.; Bhorat, Q.E.; et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N. Engl. J. Med. 2021, 384, 1885–1898. [Google Scholar] [CrossRef] [PubMed]
- Lopez Bernal, J.; Andrews, N.; Gower, C.; Gallagher, E.; Simmons, R.; Thelwall, S.; Stowe, J.; Tessier, E.; Groves, N.; Dabrera, G.; et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N. Engl. J. Med. 2021, 385, 585–594. [Google Scholar] [CrossRef] [PubMed]
- Al-Ahmad, M.; Al-Rasheed, M.; Shalaby, N.A.B. Acquired thrombotic thrombocytopenic purpura with possible association with AstraZeneca-Oxford COVID-19 vaccine. EJHaem 2021, 2, 534–536. [Google Scholar] [CrossRef] [PubMed]
- Ryan, E.; Benjamin, D.; McDonald, I.; Barrett, A.; McHugh, J.; Ryan, K.; Enright, H. AZD1222 vaccine-related coagulopathy and thrombocytopenia without thrombosis in a young female. Br. J. Haematol. 2021, 194, 553–556. [Google Scholar] [CrossRef]
- Tolboll Sorensen, A.L.; Rolland, M.; Hartmann, J.; Harboe, Z.B.; Roed, C.; Jensen, T.O.; Kolte, L.; El Fassi, D.; Hillingso, J.; Radziwon-Balicka, A.; et al. A case of thrombocytopenia and multiple thromboses after vaccination with ChAdOx1 nCoV-19 against SARS-CoV-2. Blood Adv. 2021, 5, 2569–2574. [Google Scholar] [CrossRef]
- Almufty, H.B.; Mohammed, S.A.; Abdullah, A.M.; Merza, M.A. Potential adverse effects of COVID19 vaccines among Iraqi population; a comparison between the three available vaccines in Iraq; a retrospective cross-sectional study. Diabetes Metab. Syndr. 2021, 15, 102207. [Google Scholar] [CrossRef]
- Tobaiqy, M.; Elkout, H.; MacLure, K. Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine Reported to EudraVigilance Database. Vaccines 2021, 9, 393. [Google Scholar] [CrossRef]
- Capassoni, M.; Ketabchi, S.; Cassisa, A.; Caramelli, R.; Molinu, A.A.; Galluccio, F.; Guiducci, S. AstraZeneca (AZD1222) COVID-19 vaccine-associated adverse drug event: A case report. J. Med. Virol. 2021, 93, 5718–5720. [Google Scholar] [CrossRef]
- Ramessur, R.; Saffar, N.; Czako, B.; Agarwal, A.; Batta, K. Cutaneous thrombosis associated with skin necrosis following Oxford-AstraZeneca COVID-19 vaccination. Clin. Exp. Dermatol. 2021, 46, 1610–1612. [Google Scholar] [CrossRef]
- Nagrani, P.; Jindal, R.; Goyal, D. Onset/flare of psoriasis following the ChAdOx1 nCoV-19 Corona virus vaccine (Oxford-AstraZeneca/Covishield): Report of two cases. Dermatol. Ther. 2021, 34, e15085. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Shaw, R.H.; Stuart, A.S.V.; Greenland, M.; Aley, P.K.; Andrews, N.J.; Cameron, J.C.; Charlton, S.; Clutterbuck, E.A.; Collins, A.M.; et al. Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): A single-blind, randomised, non-inferiority trial. Lancet 2021, 398, 856–869. [Google Scholar] [CrossRef]
- Tanriover, M.D.; Doganay, H.L.; Akova, M.; Guner, H.R.; Azap, A.; Akhan, S.; Kose, S.; Erdinc, F.S.; Akalin, E.H.; Tabak, O.F.; et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): Interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet 2021, 398, 213–222. [Google Scholar] [CrossRef]
- Melo-Gonzalez, F.; Soto, J.A.; Gonzalez, L.A.; Fernandez, J.; Duarte, L.F.; Schultz, B.M.; Galvez, N.M.S.; Pacheco, G.A.; Rios, M.; Vazquez, Y.; et al. Recognition of Variants of Concern by Antibodies and T Cells Induced by a SARS-CoV-2 Inactivated Vaccine. Front. Immunol. 2021, 12, 747830. [Google Scholar] [CrossRef]
- Vacharathit, V.; Aiewsakun, P.; Manopwisedjaroen, S.; Srisaowakarn, C.; Laopanupong, T.; Ludowyke, N.; Phuphuakrat, A.; Setthaudom, C.; Ekronarongchai, S.; Srichatrapimuk, S.; et al. CoronaVac induces lower neutralising activity against variants of concern than natural infection. Lancet Infect. Dis. 2021, 21, 1352–1354. [Google Scholar] [CrossRef]
- Ranzani, O.T.; Hitchings, M.D.T.; Dorion, M.; D’Agostini, T.L.; de Paula, R.C.; de Paula, O.F.P.; Villela, E.F.M.; Torres, M.S.S.; de Oliveira, S.B.; Schulz, W.; et al. Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of covid-19 in Brazil: Test negative case-control study. BMJ 2021, 374, n2015. [Google Scholar] [CrossRef]
- Perez-Then, E.; Lucas, C.; Monteiro, V.S.; Miric, M.; Brache, V.; Cochon, L.; Vogels, C.B.F.; Malik, A.A.; De la Cruz, E.; Jorge, A.; et al. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nat. Med. 2022, 28, 481–485. [Google Scholar] [CrossRef]
- Han, B.; Song, Y.; Li, C.; Yang, W.; Ma, Q.; Jiang, Z.; Li, M.; Lian, X.; Jiao, W.; Wang, L.; et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: A double-blind, randomised, controlled, phase 1/2 clinical trial. Lancet Infect. Dis. 2021, 21, 1645–1653. [Google Scholar] [CrossRef]
- Tebas, P.; Yang, S.; Boyer, J.D.; Reuschel, E.L.; Patel, A.; Christensen-Quick, A.; Andrade, V.M.; Morrow, M.P.; Kraynyak, K.; Agnes, J.; et al. Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A preliminary report of an open-label, Phase 1 clinical trial. EClinicalMedicine 2021, 31, 100689. [Google Scholar] [CrossRef]
- Riddell, S.; Goldie, S.; McAuley, A.J.; Kuiper, M.J.; Durr, P.A.; Blasdell, K.R.; Tachedjian, M.; Druce, J.D.; Smith, T.R.F.; Broderick, K.E.; et al. Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets. Front. Immunol. 2021, 12, 694857. [Google Scholar] [CrossRef]
- Dey, A.; Chozhavel Rajanathan, T.M.; Chandra, H.; Pericherla, H.P.R.; Kumar, S.; Choonia, H.S.; Bajpai, M.; Singh, A.K.; Sinha, A.; Saini, G.; et al. Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models. Vaccine 2021, 39, 4108–4116. [Google Scholar] [CrossRef] [PubMed]
- Khobragade, A.; Bhate, S.; Ramaiah, V.; Deshpande, S.; Giri, K.; Phophle, H.; Supe, P.; Godara, I.; Revanna, R.; Nagarkar, R.; et al. Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): The interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India. Lancet 2022, 399, 1313–1321. [Google Scholar] [CrossRef]
- Heath, P.T.; Galiza, E.P.; Baxter, D.N.; Boffito, M.; Browne, D.; Burns, F.; Chadwick, D.R.; Clark, R.; Cosgrove, C.; Galloway, J.; et al. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. N. Engl. J. Med. 2021, 385, 1172–1183. [Google Scholar] [CrossRef]
- Sacks, H.S. The Novavax vaccine had 90% efficacy against COVID-19 >/=7 d after the second dose. Ann. Intern. Med. 2021, 174, JC124. [Google Scholar] [CrossRef] [PubMed]
- Shinde, V.; Bhikha, S.; Hoosain, Z.; Archary, M.; Bhorat, Q.; Fairlie, L.; Lalloo, U.; Masilela, M.S.L.; Moodley, D.; Hanley, S.; et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant. N. Engl. J. Med. 2021, 384, 1899–1909. [Google Scholar] [CrossRef] [PubMed]
- Dunkle, L.M.; Kotloff, K.L.; Gay, C.L.; Anez, G.; Adelglass, J.M.; Barrat Hernandez, A.Q.; Harper, W.L.; Duncanson, D.M.; McArthur, M.A.; Florescu, D.F.; et al. Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico. N. Engl. J. Med. 2022, 386, 531–543. [Google Scholar] [CrossRef]
- Formica, N.; Mallory, R.; Albert, G.; Robinson, M.; Plested, J.S.; Cho, I.; Robertson, A.; Dubovsky, F.; Glenn, G.M.; 2019nCoV-101 Study Group. Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: A phase 2 randomized placebo-controlled trial. PLoS Med. 2021, 18, e1003769. [Google Scholar] [CrossRef]
- Abu-Raddad, L.J.; Chemaitelly, H.; Yassine, H.M.; Benslimane, F.M.; Al Khatib, H.A.; Tang, P.; Malek, J.A.; Coyle, P.; Ayoub, H.H.; Al Kanaani, Z.; et al. Pfizer-BioNTech mRNA BNT162b2 Covid-19 vaccine protection against variants of concern after one versus two doses. J. Travel Med. 2021, 28, taab083. [Google Scholar] [CrossRef]
- Dagan, N.; Barda, N.; Biron-Shental, T.; Makov-Assif, M.; Key, C.; Kohane, I.S.; Hernan, M.A.; Lipsitch, M.; Hernandez-Diaz, S.; Reis, B.Y.; et al. Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy. Nat. Med. 2021, 27, 1693–1695. [Google Scholar] [CrossRef]
- Forchette, L.; Sebastian, W.; Liu, T. A Comprehensive Review of COVID-19 Virology, Vaccines, Variants, and Therapeutics. Curr. Med. Sci. 2021, 41, 1037–1051. [Google Scholar] [CrossRef]
- Yuan, Y.; Cao, D.; Zhang, Y.; Ma, J.; Qi, J.; Wang, Q.; Lu, G.; Wu, Y.; Yan, J.; Shi, Y.; et al. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat. Commun. 2017, 8, 15092. [Google Scholar] [CrossRef] [PubMed]
- Shang, J.; Wan, Y.; Luo, C.; Ye, G.; Geng, Q.; Auerbach, A.; Li, F. Cell entry mechanisms of SARS-CoV-2. Proc. Natl. Acad. Sci. USA 2020, 117, 11727–11734. [Google Scholar] [CrossRef] [PubMed]
- Dhama, K.; Sharun, K.; Tiwari, R.; Dadar, M.; Malik, Y.S.; Singh, K.P.; Chaicumpa, W. COVID-19, an emerging coronavirus infection: Advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Hum. Vaccin. Immunother. 2020, 16, 1232–1238. [Google Scholar] [CrossRef] [PubMed]
- Chandrashekar, A.; Liu, J.; Martinot, A.J.; McMahan, K.; Mercado, N.B.; Peter, L.; Tostanoski, L.H.; Yu, J.; Maliga, Z.; Nekorchuk, M.; et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science 2020, 369, 812–817. [Google Scholar] [CrossRef] [PubMed]
- Gottlieb, R.L.; Nirula, A.; Chen, P.; Boscia, J.; Heller, B.; Morris, J.; Huhn, G.; Cardona, J.; Mocherla, B.; Stosor, V.; et al. Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA 2021, 325, 632–644. [Google Scholar] [CrossRef]
- Garcia-Beltran, W.F.; Lam, E.C.; Astudillo, M.G.; Yang, D.; Miller, T.E.; Feldman, J.; Hauser, B.M.; Caradonna, T.M.; Clayton, K.L.; Nitido, A.D.; et al. COVID-19-neutralizing antibodies predict disease severity and survival. Cell 2021, 184, 476–488e411. [Google Scholar] [CrossRef]
- Harvey, W.T.; Carabelli, A.M.; Jackson, B.; Gupta, R.K.; Thomson, E.C.; Harrison, E.M.; Ludden, C.; Reeve, R.; Rambaut, A.; Consortium, C.-G.U.; et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 2021, 19, 409–424. [Google Scholar] [CrossRef]
- Shiakolas, A.R.; Kramer, K.J.; Wrapp, D.; Richardson, S.I.; Schafer, A.; Wall, S.; Wang, N.; Janowska, K.; Pilewski, K.A.; Venkat, R.; et al. Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions. Cell Rep. Med. 2021, 2, 100313. [Google Scholar] [CrossRef]
- Wang, C.; van Haperen, R.; Gutierrez-Alvarez, J.; Li, W.; Okba, N.M.A.; Albulescu, I.; Widjaja, I.; van Dieren, B.; Fernandez-Delgado, R.; Sola, I.; et al. A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies. Nat. Commun. 2021, 12, 1715. [Google Scholar] [CrossRef]
- Poh, C.M.; Carissimo, G.; Wang, B.; Amrun, S.N.; Lee, C.Y.; Chee, R.S.; Fong, S.W.; Yeo, N.K.; Lee, W.H.; Torres-Ruesta, A.; et al. Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients. Nat. Commun. 2020, 11, 2806. [Google Scholar] [CrossRef]
- McMahan, K.; Yu, J.; Mercado, N.B.; Loos, C.; Tostanoski, L.H.; Chandrashekar, A.; Liu, J.; Peter, L.; Atyeo, C.; Zhu, A.; et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature 2021, 590, 630–634. [Google Scholar] [CrossRef] [PubMed]
- Hooper, N.M.; Lambert, D.W.; Turner, A.J. Discovery and characterization of ACE2—A 20-year journey of surprises from vasopeptidase to COVID-19. Clin. Sci. 2020, 134, 2489–2501. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Li, S.; Huang, Y.; Chen, H.; Zhang, S.; Zhang, Z.; Wu, W.; Zeng, X.; Zhou, B.; Li, B. Secreted Expression of mRNA-Encoded Truncated ACE2 Variants for SARS-CoV-2 via Lipid-Like Nanoassemblies. Adv. Mater. 2021, 33, e2101707. [Google Scholar] [CrossRef] [PubMed]
- Das, J.K.; Roy, S. A study on non-synonymous mutational patterns in structural proteins of SARS-CoV-2. Genome 2021, 64, 665–678. [Google Scholar] [CrossRef] [PubMed]
- Muralidar, S.; Ambi, S.V.; Sekaran, S.; Krishnan, U.M. The emergence of COVID-19 as a global pandemic: Understanding the epidemiology, immune response and potential therapeutic targets of SARS-CoV-2. Biochimie 2020, 179, 85–100. [Google Scholar] [CrossRef]
- Chung, M.K.; Karnik, S.; Saef, J.; Bergmann, C.; Barnard, J.; Lederman, M.M.; Tilton, J.; Cheng, F.; Harding, C.V.; Young, J.B.; et al. SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy. EBioMedicine 2020, 58, 102907. [Google Scholar] [CrossRef]
- Sharma, R.K.; Stevens, B.R.; Obukhov, A.G.; Grant, M.B.; Oudit, G.Y.; Li, Q.; Richards, E.M.; Pepine, C.J.; Raizada, M.K. ACE2 (Angiotensin-Converting Enzyme 2) in Cardiopulmonary Diseases: Ramifications for the Control of SARS-CoV-2. Hypertension 2020, 76, 651–661. [Google Scholar] [CrossRef]
- Marquez, A.; Wysocki, J.; Pandit, J.; Batlle, D. An update on ACE2 amplification and its therapeutic potential. Acta Physiol. 2021, 231, e13513. [Google Scholar] [CrossRef]
- Mehrabadi, M.E.; Hemmati, R.; Tashakor, A.; Homaei, A.; Yousefzadeh, M.; Hemati, K.; Hosseinkhani, S. Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity. Biomed. Pharmacother. 2021, 137, 111363. [Google Scholar] [CrossRef]
- Hemnes, A.R.; Rathinasabapathy, A.; Austin, E.A.; Brittain, E.L.; Carrier, E.J.; Chen, X.; Fessel, J.P.; Fike, C.D.; Fong, P.; Fortune, N.; et al. A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension. Eur. Respir. J. 2018, 51, 1702638. [Google Scholar] [CrossRef]
- Xiao, L.; Sakagami, H.; Miwa, N. ACE2: The key Molecule for Understanding the Pathophysiology of Severe and Critical Conditions of COVID-19: Demon or Angel? Viruses 2020, 12, 491. [Google Scholar] [CrossRef] [PubMed]
- Verdecchia, P.; Cavallini, C.; Spanevello, A.; Angeli, F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur. J. Intern. Med. 2020, 76, 14–20. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Penninger, J.M.; Li, Y.; Zhong, N.; Slutsky, A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target. Intensive. Care Med. 2020, 46, 586–590. [Google Scholar] [CrossRef]
- Ziegler, C.G.K.; Allon, S.J.; Nyquist, S.K.; Mbano, I.M.; Miao, V.N.; Tzouanas, C.N.; Cao, Y.; Yousif, A.S.; Bals, J.; Hauser, B.M.; et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell 2020, 181, 1016–1035 e1019. [Google Scholar] [CrossRef] [PubMed]
- Abd El-Aziz, T.M.; Al-Sabi, A.; Stockand, J.D. Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID-19. Signal. Transduct. Target. Ther. 2020, 5, 258. [Google Scholar] [CrossRef]
- Monteil, V.; Kwon, H.; Prado, P.; Hagelkruys, A.; Wimmer, R.A.; Stahl, M.; Leopoldi, A.; Garreta, E.; Hurtado Del Pozo, C.; Prosper, F.; et al. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell 2020, 181, 905–913e907. [Google Scholar] [CrossRef]
- Zoufaly, A.; Poglitsch, M.; Aberle, J.H.; Hoepler, W.; Seitz, T.; Traugott, M.; Grieb, A.; Pawelka, E.; Laferl, H.; Wenisch, C.; et al. Human recombinant soluble ACE2 in severe COVID-19. Lancet Respir. Med. 2020, 8, 1154–1158. [Google Scholar] [CrossRef]
- Monteil, V.; Dyczynski, M.; Lauschke, V.M.; Kwon, H.; Wirnsberger, G.; Youhanna, S.; Zhang, H.; Slutsky, A.S.; Hurtado Del Pozo, C.; Horn, M.; et al. Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection. EMBO Mol. Med. 2021, 13, e13426. [Google Scholar] [CrossRef]
- El-Shennawy, L.; Hoffmann, A.D.; Dashzeveg, N.K.; McAndrews, K.M.; Mehl, P.J.; Cornish, D.; Yu, Z.; Tokars, V.L.; Nicolaescu, V.; Tomatsidou, A.; et al. Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2. Nat. Commun. 2022, 13, 405. [Google Scholar] [CrossRef]
- Li, X.; Yang, X.; Chang, L.; Wang, Z.; Wang, T.; Zhang, Z.; Bai, J.; Liang, R.; Niu, Q.; Zhang, H. Endoplasmic reticulum rather than mitochondria plays a major role in the neuronal apoptosis induced by polybrominated diphenyl ether-153. Toxicol. Lett. 2019, 311, 37–48. [Google Scholar] [CrossRef]
- Chauhan, N.; Jaggi, M.; Chauhan, S.C.; Yallapu, M.M. COVID-19: Fighting the invisible enemy with microRNAs. Expert. Rev. Anti. Infect. Ther. 2021, 19, 137–145. [Google Scholar] [CrossRef] [PubMed]
- Bozgeyik, I. Therapeutic potential of miRNAs targeting SARS-CoV-2 host cell receptor ACE2. Meta Gene 2021, 27, 100831. [Google Scholar] [CrossRef] [PubMed]
- Fajgenbaum, D.C.; June, C.H. Cytokine Storm. N. Engl. J. Med. 2020, 383, 2255–2273. [Google Scholar] [CrossRef] [PubMed]
- Lopez, C.B.; Moran, T.M.; Schulman, J.L.; Fernandez-Sesma, A. Antiviral immunity and the role of dendritic cells. Int. Rev. Immunol. 2002, 21, 339–353. [Google Scholar] [CrossRef]
- Rabiu Abubakar, A.; Ahmad, R.; Rowaiye, A.B.; Rahman, S.; Iskandar, K.; Dutta, S.; Oli, A.N.; Dhingra, S.; Tor, M.A.; Etando, A.; et al. Targeting Specific Checkpoints in the Management of SARS-CoV-2 Induced Cytokine Storm. Life 2022, 12, 478. [Google Scholar] [CrossRef]
- Rangchaikul, P.; Venketaraman, V. SARS-CoV-2 and the Immune Response in Pregnancy with Delta Variant Considerations. Infect. Dis. Rep. 2021, 13, 993–1008. [Google Scholar] [CrossRef]
- Moubarak, M.; Kasozi, K.I.; Hetta, H.F.; Shaheen, H.M.; Rauf, A.; Al-Kuraishy, H.M.; Qusti, S.; Alshammari, E.M.; Ayikobua, E.T.; Ssempijja, F.; et al. The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections. Life 2021, 11, 734. [Google Scholar] [CrossRef]
- Hirano, T. IL-6 in inflammation, autoimmunity and cancer. Int. Immunol. 2021, 33, 127–148. [Google Scholar] [CrossRef]
- Broman, N.; Rantasarkka, K.; Feuth, T.; Valtonen, M.; Waris, M.; Hohenthal, U.; Rintala, E.; Karlsson, A.; Marttila, H.; Peltola, V.; et al. IL-6 and other biomarkers as predictors of severity in COVID-19. Ann. Med. 2021, 53, 410–412. [Google Scholar] [CrossRef]
- Coomes, E.A.; Haghbayan, H. Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev. Med. Virol. 2020, 30, 1–9. [Google Scholar] [CrossRef]
- Cortegiani, A.; Ippolito, M.; Greco, M.; Granone, V.; Protti, A.; Gregoretti, C.; Giarratano, A.; Einav, S.; Cecconi, M. Rationale and evidence on the use of tocilizumab in COVID-19: A systematic review. Pulmonology 2021, 27, 52–66. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Montalva, A.; Sellares-Nadal, J.; Espinosa-Pereiro, J.; Fernandez-Hidalgo, N.; Perez-Hoyos, S.; Salvador, F.; Dura, X.; Miarons, M.; Anton, A.; Eremiev-Eremiev, S.; et al. Early outcomes in adults hospitalized with severe SARS-CoV-2 infection receiving tocilizumab. Med. Clin. 2022, 158, 509–518. [Google Scholar] [CrossRef] [PubMed]
- Alex, R.; Gulam, S.M.; Kumar, K. Real-Life Use of Tocilizumab in the Treatment of Severe COVID-19 Pneumonia. Adv. Virol. 2022, 2022, 7060466. [Google Scholar] [CrossRef] [PubMed]
- Godolphin, P.J.; Fisher, D.J.; Berry, L.R.; Derde, L.P.G.; Diaz, J.V.; Gordon, A.C.; Lorenzi, E.; Marshall, J.C.; Murthy, S.; Shankar-Hari, M.; et al. Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis. PLoS ONE 2022, 17, e0270668. [Google Scholar] [CrossRef]
- Mady, A.F.; Abdulrahman, B.; Mumtaz, S.A.; Al-Odat, M.A.; Kuhail, A.; Altoraifi, R.; Alshae, R.; Alharthy, A.M.; Aletreby, W.T. “Ventilator-free days” composite outcome in patients with SARS-CoV-2 infection treated with tocilizumab: A retrospective competing risk analysis. Heart Lung 2022, 56, 118–124. [Google Scholar] [CrossRef] [PubMed]
- Chowdhry, M.; Hussain, M.; Singh, P.; Lekshmi, M.; Agrawal, S.; Kanwar, M.S.; Chawla, R.; Kantroo, V.; Bali, R.; Bansal, A.; et al. Convalescent plasma—An insight into a novel treatment of COVID-19 ICU patients. Transfus. Apher. Sci. 2022, 103497. [Google Scholar] [CrossRef]
- Narazaki, M.; Kishimoto, T. Current status and prospects of IL-6-targeting therapy. Expert. Rev. Clin. Pharmacol. 2022, 15, 575–592. [Google Scholar] [CrossRef]
- Cai, S.; Sun, W.; Li, M.; Dong, L. A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab. Clin. Rheumatol. 2020, 39, 2797–2802. [Google Scholar] [CrossRef] [PubMed]
- Yamada, Z.; Nanki, T. COVID-19 in a Patient With Rheumatoid Arthritis During Tocilizumab Treatment. J. Clin. Rheumatol. 2020, 26, 240–241. [Google Scholar] [CrossRef]
- Saad, E.; Awadelkarim, A.; Agab, M.; Babkir, A. Tocilizumab-Associated Small Bowel Perforation in a Young Patient With Rheumatoid Arthritis: A Lesson to Remember During COVID-19 Pandemic. J. Med. Cases 2022, 13, 135–139. [Google Scholar] [CrossRef]
- Kizilkilic, E.K.; Unkun, R.; Uygunoglu, U.; Delil, S.; Ozkara, C. Treatment of COVID-19-induced refractory status epilepticus by tocilizumab. Eur. J. Neurol. 2022, 29, 2861–2863. [Google Scholar] [CrossRef]
- Conti, P.; Gallenga, C.E.; Tete, G.; Caraffa, A.; Ronconi, G.; Younes, A.; Toniato, E.; Ross, R.; Kritas, S.K. How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1. J. Biol. Regul. Homeost. Agents 2020, 34, 333–338. [Google Scholar]
- Russell, B.; Moss, C.; George, G.; Santaolalla, A.; Cope, A.; Papa, S.; Van Hemelrijck, M. Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience 2020, 14, 1022. [Google Scholar] [CrossRef]
- Wang, F.; Huang, S.; Gao, R.; Zhou, Y.; Lai, C.; Li, Z.; Xian, W.; Qian, X.; Li, Z.; Huang, Y.; et al. Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility. Cell Discov. 2020, 6, 83. [Google Scholar] [CrossRef]
- Mardi, A.; Meidaninikjeh, S.; Nikfarjam, S.; Majidi Zolbanin, N.; Jafari, R. Interleukin-1 in COVID-19 Infection: Immunopathogenesis and Possible Therapeutic Perspective. Viral. Immunol. 2021, 34, 679–688. [Google Scholar] [CrossRef]
- Kyriazopoulou, E.; Huet, T.; Cavalli, G.; Gori, A.; Kyprianou, M.; Pickkers, P.; Eugen-Olsen, J.; Clerici, M.; Veas, F.; Chatellier, G.; et al. Effect of anakinra on mortality in patients with COVID-19: A systematic review and patient-level meta-analysis. Lancet Rheumatol. 2021, 3, e690–e697. [Google Scholar] [CrossRef]
- Kyriazopoulou, E.; Poulakou, G.; Milionis, H.; Metallidis, S.; Adamis, G.; Tsiakos, K.; Fragkou, A.; Rapti, A.; Damoulari, C.; Fantoni, M.; et al. Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: A double-blind, randomized controlled phase 3 trial. Nat. Med. 2021, 27, 1752–1760. [Google Scholar] [CrossRef]
- Kooistra, E.J.; Waalders, N.J.B.; Grondman, I.; Janssen, N.A.F.; de Nooijer, A.H.; Netea, M.G.; van de Veerdonk, F.L.; Ewalds, E.; van der Hoeven, J.G.; Kox, M.; et al. Anakinra treatment in critically ill COVID-19 patients: A prospective cohort study. Crit. Care 2020, 24, 688. [Google Scholar] [CrossRef]
- Huet, T.; Beaussier, H.; Voisin, O.; Jouveshomme, S.; Dauriat, G.; Lazareth, I.; Sacco, E.; Naccache, J.M.; Bezie, Y.; Laplanche, S.; et al. Anakinra for severe forms of COVID-19: A cohort study. Lancet Rheumatol. 2020, 2, e393–e400. [Google Scholar] [CrossRef]
- Cavalli, G.; De Luca, G.; Campochiaro, C.; Della-Torre, E.; Ripa, M.; Canetti, D.; Oltolini, C.; Castiglioni, B.; Tassan Din, C.; Boffini, N.; et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: A retrospective cohort study. Lancet Rheumatol. 2020, 2, e325–e331. [Google Scholar] [CrossRef]
- Kyriazopoulou, E.; Panagopoulos, P.; Metallidis, S.; Dalekos, G.N.; Poulakou, G.; Gatselis, N.; Karakike, E.; Saridaki, M.; Loli, G.; Stefos, A.; et al. An open label trial of anakinra to prevent respiratory failure in COVID-19. Elife 2021, 10, e66125. [Google Scholar] [CrossRef]
- Schett, G.; Manger, B.; Simon, D.; Caporali, R. COVID-19 revisiting inflammatory pathways of arthritis. Nat. Rev. Rheumatol. 2020, 16, 465–470. [Google Scholar] [CrossRef]
- Zhao, H.; Wu, L.; Yan, G.; Chen, Y.; Zhou, M.; Wu, Y.; Li, Y. Inflammation and tumor progression: Signaling pathways and targeted intervention. Signal Transduct. Target. Ther. 2021, 6, 263. [Google Scholar] [CrossRef]
- Karki, R.; Sharma, B.R.; Tuladhar, S.; Williams, E.P.; Zalduondo, L.; Samir, P.; Zheng, M.; Sundaram, B.; Banoth, B.; Malireddi, R.K.S.; et al. Synergism of TNF-alpha and IFN-gamma Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell 2021, 184, 149–168e117. [Google Scholar] [CrossRef]
- Fakharian, A.; Barati, S.; Mirenayat, M.; Rezaei, M.; Haseli, S.; Torkaman, P.; Yousefian, S.; Dastan, A.; Jamaati, H.; Dastan, F. Evaluation of adalimumab effects in managing severe cases of COVID-19: A randomized controlled trial. Int. Immunopharmacol. 2021, 99, 107961. [Google Scholar] [CrossRef]
- Shi, Z.; Puyo, C.A. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Ther. Clin. Risk Manag. 2020, 16, 1047–1055. [Google Scholar] [CrossRef]
- De Flora, S.; Balansky, R.; La Maestra, S. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J. 2020, 34, 13185–13193. [Google Scholar] [CrossRef]
- Zhou, N.; Yang, X.; Huang, A.; Chen, Z. The Potential Mechanism of N-acetylcysteine in Treating COVID-19. Curr. Pharm. Biotechnol. 2021, 22, 1584–1590. [Google Scholar] [CrossRef]
- El-Ashmawy, N.E.; Lashin, A.A.; Okasha, K.M.; Abo Kamer, A.M.; Mostafa, T.M.; El-Aasr, M.; Goda, A.E.; Haggag, Y.A.; Tawfik, H.O.; Abo-Saif, M.A. The plausible mechanisms of tramadol for treatment of COVID-19. Med. Hypotheses 2021, 146, 110468. [Google Scholar] [CrossRef]
- Owen, D.R.; Allerton, C.M.N.; Anderson, A.S.; Aschenbrenner, L.; Avery, M.; Berritt, S.; Boras, B.; Cardin, R.D.; Carlo, A.; Coffman, K.J.; et al. An oral SARS-CoV-2 M(pro) inhibitor clinical candidate for the treatment of COVID-19. Science 2021, 374, 1586–1593. [Google Scholar] [CrossRef]
- Frediansyah, A.; Sofyantoro, F.; Alhumaid, S.; Al Mutair, A.; Albayat, H.; Altaweil, H.I.; Al-Afghani, H.M.; AlRamadhan, A.A.; AlGhazal, M.R.; Turkistani, S.A.; et al. Microbial Natural Products with Antiviral Activities, Including Anti-SARS-CoV-2: A Review. Molecules 2022, 27, 4305. [Google Scholar] [CrossRef]
- Hung, Y.P.; Lee, J.C.; Chiu, C.W.; Lee, C.C.; Tsai, P.J.; Hsu, I.L.; Ko, W.C. Oral Nirmatrelvir/Ritonavir Therapy for COVID-19: The Dawn in the Dark? Antibiotics 2022, 11, 220. [Google Scholar] [CrossRef]
- Singh, R.S.P.; Toussi, S.S.; Hackman, F.; Chan, P.L.; Rao, R.; Allen, R.; Van Eyck, L.; Pawlak, S.; Kadar, E.P.; Clark, F.; et al. Innovative Randomized Phase I Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir. Clin. Pharmacol. Ther. 2022, 112, 101–111. [Google Scholar] [CrossRef]
- Ullrich, S.; Ekanayake, K.B.; Otting, G.; Nitsche, C. Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir. Bioorg. Med. Chem. Lett. 2022, 62, 128629. [Google Scholar] [CrossRef]
- Abdelnabi, R.; Foo, C.S.; Jochmans, D.; Vangeel, L.; De Jonghe, S.; Augustijns, P.; Mols, R.; Weynand, B.; Wattanakul, T.; Hoglund, R.M.; et al. The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern. Nat. Commun. 2022, 13, 719. [Google Scholar] [CrossRef]
- Senapati, S.; Banerjee, P.; Bhagavatula, S.; Kushwaha, P.P.; Kumar, S. Contributions of human ACE2 and TMPRSS2 in determining host-pathogen interaction of COVID-19. J. Genet. 2021, 100, 1–16. [Google Scholar] [CrossRef]
- Laurian, C. Arteriopathy caused by radiation. J. Mal. Vasc. 1986, 11, 16–18. [Google Scholar]
- Zhao, H.; Lu, L.; Peng, Z.; Chen, L.L.; Meng, X.; Zhang, C.; Ip, J.D.; Chan, W.M.; Chu, A.W.; Chan, K.H.; et al. SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells. Emerg. Microbes Infect. 2022, 11, 277–283. [Google Scholar] [CrossRef]
- Hoffmann, M.; Hofmann-Winkler, H.; Smith, J.C.; Kruger, N.; Arora, P.; Sorensen, L.K.; Sogaard, O.S.; Hasselstrom, J.B.; Winkler, M.; Hempel, T.; et al. Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity. EBioMedicine 2021, 65, 103255. [Google Scholar] [CrossRef]
- Chupp, G.; Spichler-Moffarah, A.; Sogaard, O.S.; Esserman, D.; Dziura, J.; Danzig, L.; Chaurasia, R.; Patra, K.P.; Salovey, A.; Nunez, A.; et al. A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste. medRxiv, 2022; preprint. [Google Scholar]
- Terada, J.; Fujita, R.; Kawahara, T.; Hirasawa, Y.; Kinoshita, T.; Takeshita, Y.; Isaka, Y.; Kinouchi, T.; Tajima, H.; Tada, Y.; et al. Favipiravir, camostat, and ciclesonide combination therapy in patients with moderate COVID-19 pneumonia with/without oxygen therapy: An open-label, single-center phase 3 randomized clinical trial. EClinicalMedicine 2022, 49, 101484. [Google Scholar] [CrossRef]
- Tobback, E.; Degroote, S.; Buysse, S.; Delesie, L.; Van Dooren, L.; Vanherrewege, S.; Barbezange, C.; Hutse, V.; Romano, M.; Thomas, I.; et al. Efficacy and safety of camostat mesylate in early COVID-19 disease in an ambulatory setting: A randomized placebo-controlled phase II trial. Int. J. Infect. Dis. 2022, 122, 628–635. [Google Scholar] [CrossRef]
- Zhu, H.; Du, W.; Song, M.; Liu, Q.; Herrmann, A.; Huang, Q. Spontaneous binding of potential COVID-19 drugs (Camostat and Nafamostat) to human serine protease TMPRSS2. Comput. Struct. Biotechnol. J. 2021, 19, 467–476. [Google Scholar] [CrossRef]
- Li, K.; Meyerholz, D.K.; Bartlett, J.A.; McCray, P.B., Jr. The TMPRSS2 Inhibitor Nafamostat Reduces SARS-CoV-2 Pulmonary Infection in Mouse Models of COVID-19. mBio 2021, 12, e0097021. [Google Scholar] [CrossRef]
Variants | Strain Name | First Reported Place | First Reported Time | Main S Protein Mutation |
---|---|---|---|---|
Alpha | B.1.1.7 | United Kingdom | December 2020 | ΔH69, ΔV70, Δ144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H |
Beta | B.1.351 | South Africa | October 2020 | D80A, D215G, Δ241, Δ242, Δ243, V367F, P384L, R408I, K417N, E484K, N501Y, D614G, A701V |
Gamma | P.1 | Japan/Brazil | January 2020 | L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F |
Delta | B.1.617.2 | India | December 2020 | T19R, T95I, G142D, R158G, K417N, L452R, T478K, D614G, P681R, D950N |
Omicron | B.1.1.529 | South Africa | November 2021 | A67V, ΔH69, ΔV70, T95I, G142D, ΔV143, ΔY144, ΔY145, ΔN211, L212I, ins214EPE, G339D, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, N679K, P681H, N764K, D796Y, Q954H, N969K, L981F, and N856K |
Lambda | C.37/B.1.1.1 | Peru | August 2020 | G75V, T76I, Δ246–252 (1246–252), L452Q, F490S, D614G and T859N |
Mu | B.1.621 | Colombia | January 2021 | Y144T, Y145S, R346K, E484K, N501Y and P681H |
Kappa | B.1.617.1 | India | December 2021 | L452R, T478K, E484Q, D614G, and P681R |
Vaccine | Platform | Antigen | Efficacy of Infection | Immune Type | Sponsor Location |
---|---|---|---|---|---|
Pfizer/BioNTech mRNA vaccine | mRNA | Full-length S protein | 95% in WT infection [77]; 89.5–93.7% (Alpha) [121]; 75–100% (Beta) [77]; 52.4–88% (Delta) [88]; 22.5% (Omicron) [122] | Humoral immunity | Germany |
Moderna mRNA-1273 vaccine | mRNA | Segments of SARS-CoV-2 hereditary material/ Stabilized Spike | 94.1% in WT infection [85]; 89% (Alpha); 85% (Gamma) [87]; 96.4% (Beta) [86]; 50.6% (Delta) [88] | Humoral and cellular immunity | USA |
AZD1222 vaccine | Viral vector | Whole-length S protein | 62.1–79% in WT infection [93,94]; 74.5 (Alpha); 67% (Delta) [96]; 10.4% (Beta) [95] | Cellular immunity | UK |
CoronaVac vaccine | Inactivated virus | Inactivated whole SARS-CoV-2 virus | 83.5% in WT infection in patients aged 18–59 [106]; 75–88.1% (Alpha), 64.2–70% (Beta), 88.1% (Gamma), 48.33–78.6% (Delta) [107] | Humoral immunity | China |
DNA vaccine | DNA | Plasmid DNA carrying S gene of SARS-CoV-2 | 66.6% of ZyCoV-D vaccine in WT infection [115] | Humoral and cellular immunity | USA/India |
NVX CoV-2373 vaccine | Protein subunit | SARS-CoV-2 S protein | 89.7% in WT infection [116]; 86.3% (Alpha) [116]; 43% (Gamma) [87] | Humoral immunity | USA |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Liang, H.-Y.; Wu, Y.; Yau, V.; Yin, H.-X.; Lowe, S.; Bentley, R.; Ahmed, M.A.; Zhao, W.; Sun, C. SARS-CoV-2 Variants, Current Vaccines and Therapeutic Implications for COVID-19. Vaccines 2022, 10, 1538. https://doi.org/10.3390/vaccines10091538
Liang H-Y, Wu Y, Yau V, Yin H-X, Lowe S, Bentley R, Ahmed MA, Zhao W, Sun C. SARS-CoV-2 Variants, Current Vaccines and Therapeutic Implications for COVID-19. Vaccines. 2022; 10(9):1538. https://doi.org/10.3390/vaccines10091538
Chicago/Turabian StyleLiang, Hong-Yu, Yuyan Wu, Vicky Yau, Huan-Xin Yin, Scott Lowe, Rachel Bentley, Mubashir Ayaz Ahmed, Wenjing Zhao, and Chenyu Sun. 2022. "SARS-CoV-2 Variants, Current Vaccines and Therapeutic Implications for COVID-19" Vaccines 10, no. 9: 1538. https://doi.org/10.3390/vaccines10091538
APA StyleLiang, H. -Y., Wu, Y., Yau, V., Yin, H. -X., Lowe, S., Bentley, R., Ahmed, M. A., Zhao, W., & Sun, C. (2022). SARS-CoV-2 Variants, Current Vaccines and Therapeutic Implications for COVID-19. Vaccines, 10(9), 1538. https://doi.org/10.3390/vaccines10091538