COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies
Abstract
:1. Introduction
2. Diagnosis, Variants and Vaccines
2.1. Diagnosis
2.2. Mutations and Variants
2.3. Vaccines for COVID-19
3. Current Therapies
4. Alternative Therapies
5. Repositioning Drugs
6. Recent Preclinical Studies
7. Recent Clinical Studies
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ACE2 | Angiotensin II receptor |
ALI | Acute lung injury |
ARDS | Acute respiratory distress syndrome |
BSAAs | Broad-spectrum antiviral agents |
CCTI | Chest computer tomography image |
CDC | Centers for Disease Control and Prevention |
CDSCO | Central Drugs Standard Control Organization |
COVID-19 | Coronavirus Disease 2019 |
CPE | Cytopathic effects |
CRS | Cytokine release syndrome |
CS | “Cytokine storm” |
CT | Computed tomography |
CXI | Chest X-ray image |
DABK | Bradykinin metabolite [des-Arg973] BK |
DCGI | Drugs Controller General of India |
EGCG | Epigallocatechin gallate |
ECDC | European Centre for Disease Prevention |
EMA | European Medicines Agency |
EUA | Emergency Use Authorization |
FBSED | Fourier-Bessel series expansion-based decomposition |
FDA | Food and Drug Administration |
GBS | Guillain-Barre syndrome |
GCG | Gallocatechingallate |
GISAID | Global Initiative on Sharing All Influenza Data |
HDIVC | High-dose intravenous vitamin C |
hERG | Human ether-ago-go-related gene |
HRQoL | Health-related quality of life |
HZ | Herpes zoster |
IFNAR | Human interferon alpha-receptor |
IFN | Interferon |
IgY | Immunoglobulin Y |
IL | Interleukin |
IVM | Ivermectin |
LQTS | Long QT syndrome |
MDR | Multidrug resistance |
MFDS | Ministry of Food and Drug Safety |
MHLW | Ministry of Health, Labour, and Welfare |
Mpro | Main protease |
NLR | Neutrophil to lymphocyte ratio |
NMPA | National Medical Products Administration |
NRA | National Regulatory Agency |
PARP1 | Poly-ADP-ribose polymerase 1 |
PCS | Post-acute COVID-19 syndrome |
PMDA | Pharmaceuticals and Medical Devices Agency |
RBD | Receptor-binding domain |
RdRp | RNA-dependent RNA polymerase |
RT-PCR | Reverse transcriptase-polymerase chain reaction |
SARS-CoV-2 | Severe acute respiratory syndrome coronavirus 2 |
TGA | Therapeutic Goods Administration |
TNF-α | Tumor necrosis factor-α |
VEGF | Vascular endothelial growth factor |
VOCs | Variants of concern |
VOIs | Variants of interest |
VST | Venous sinus thrombosis |
VZV | Varicella zoster virus |
WHO | World Health Organization |
References
- Cascella, M.; Rajnik, M.; Cuomo, A.; Dulebohn, S.C.; Di Napoli, R. Features, evaluation and treatment of Coronavirus (COVID-19). In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2020. [Google Scholar]
- WHO Coronavirus (COVID-19) Dashboard. Available online: http://covid19.who.int (accessed on 1 February 2022).
- Pisano, G.P.; Sadun, R.; Zanini, M. Lessons from Italy’s Response to Coronavirus. Available online: https://hbr.org/2020/03/lessons-from-italys-response-to-coronavirus (accessed on 24 January 2022).
- Padma, T.V. COVID Vaccines to Reach Poorest Countries in 2023—Despite Recent Pledges. Nature 2021, 595, 342–343. [Google Scholar] [CrossRef] [PubMed]
- Burki, T. Booster shots for COVID-19—The debate continues. Lancet Infect. Dis. 2021, 21, 1359–1360. [Google Scholar] [CrossRef]
- Mahase, E. COVID-19: What new variants are emerging and how are they being investigated? BMJ 2021, 372, 158. [Google Scholar] [CrossRef]
- Malik, P.; Patel, K.; Pinto, C.; Jaiswal, R.; Tirupathi, R.; Pillai, S.; Patel, U. Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)—A systematic review and meta-analysis. J. Med. Virol. 2022, 94, 253–262. [Google Scholar] [CrossRef] [PubMed]
- Cascella, M.; De Blasio, E. Neurological, psychological, and cognitive manifestations of long-COVID. In Features and Management of Acute and Chronic Neuro-COVID; Springer: Cham, Switzerland, 2022; pp. 137–158. [Google Scholar]
- Baig, A.M. Counting the neurological cost of COVID-19. Nat. Rev. Neurol. 2022, 18, 5–6. [Google Scholar] [CrossRef] [PubMed]
- Moore, P.; Esmail, F.; Qin, S.; Nand, S.; Berg, S. Hypercoagulability of COVID-19 and neurological complications: A review. J. Stroke Cerebrovasc. Dis. 2022, 31, 106163. [Google Scholar] [CrossRef]
- Walls, A.C.; Park, Y.-J.; Tortorici, M.A.; Wall, A.; McGuire, A.T.; Veesler, D. Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020, 181, 281–292. [Google Scholar] [CrossRef]
- Uddin, M.; Mustafa, F.; Rizvi, T.A.; Loney, T.; Al Suwaidi, H.; Al-Marzouqi, A.H.H.; Eldin, A.K.; Alsabeeha, N.; Adrian, T.E.; Stefanini, C.; et al. SARS-CoV-2/COVID-19: Viral genomics, epidemiology, vaccines, and therapeutic interventions. Viruses 2020, 12, 526. [Google Scholar] [CrossRef]
- Liguoro, I.; Pilotto, C.; Bonanni, M.; Ferrari, M.E.; Pusiol, A.; Nocerino, A.; Vidal, E.; Cogo, P. SARS-CoV-2 infection in children and newborns: A systematic review. Eur. J. Pediatr. 2020, 179, 1029–1046. [Google Scholar] [CrossRef]
- Principi, N.; Esposito, S. Is the Immunization of Pregnant Women against COVID-19 Justified? Vaccines 2021, 9, 970. [Google Scholar] [CrossRef]
- Mahase, E. COVID-19: Where are we on vaccines and variants? BMJ 2021, 372, 597. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Han, J. Will the COVID-19 pandemic end with the Delta and Omicron variants? Environ. Chem. Lett. 2022, 1–11. [Google Scholar] [CrossRef]
- Baraniuk, C. COVID-19: How effective are vaccines against the Delta variant? BMJ 2021, 374. [Google Scholar] [CrossRef] [PubMed]
- Rebold, N.; Holger, D.; Alosaimy, S.; Morrisette, T.; Rybak, M. COVID-19: Before the fall, an evidence-based narrative review of treatment options. Infect. Dis. Ther. 2021, 10, 93–113. [Google Scholar] [CrossRef] [PubMed]
- Lawton, G. Are booster shots coming? New Sci. 2021, 250, 8–9. [Google Scholar] [CrossRef]
- Mahase, E. COVID-19 booster vaccines: What we know and who’s doing what. BMJ 2021, 374, n2082. [Google Scholar] [CrossRef]
- Quilty, B.J.; Clifford, S.; Hellewell, J.; Russell, T.W.; Kucharski, A.J.; Flasche, S.; Edmunds, W.J.; Atkins, K.E.; Foss, A.M.; Waterlow, N.R.; et al. Quarantine and testing strategies in contact tracing for SARS-CoV-2: A modelling study. Lancet Public Health 2021, 6, e175–e183. [Google Scholar] [CrossRef]
- Killgore, W.D.; Cloonan, S.A.; Taylor, E.C.; Vanuk, J.R.; Dailey, N.S. Morning drinking during COVID-19 lockdowns. Psychiatry Res. 2022, 307, 114320. [Google Scholar] [CrossRef]
- Schmidt, R.A.; Genois, R.; Jin, J.; Vigo, D.; Rehm, J.; Rush, B. The early impact of COVID-19 on the incidence, prevalence, and severity of alcohol use and other drugs: A systematic review. Drug Alcohol Depend. 2021, 228, 109065. [Google Scholar] [CrossRef]
- Feuillet, V.; Canard, B.; Trautmann, A. Combining antivirals and immunomodulators to fight COVID-19. Trends Immunol. 2021, 42, 31–44. [Google Scholar] [CrossRef]
- Romanou, V.; Koukaki, E.; Chantziara, V.; Stamou, P.; Kote, A.; Vasileiadis, I.; Koutsoukou, A.; Rovina, N. Dexamethasone in the Treatment of COVID-19: Primus Inter Pares? J. Pers. Med. 2021, 11, 556. [Google Scholar] [CrossRef] [PubMed]
- Malone, B.; Campbell, E.A. Molnupiravir: Coding for catastrophe. Nat. Struct. Mol. Biol. 2021, 28, 706–708. [Google Scholar] [CrossRef] [PubMed]
- Cave, J.A.; Phizackerley, D. Molnupiravir: Evidence by press release. Drug Ther. Bull. 2022, 60, 2. [Google Scholar] [CrossRef] [PubMed]
- Dyer, O. COVID-19: Doctors will refuse to limit use of antiviral drug to unvaccinated patients, say ethicists. Br. Med. J. Publ. Group 2021, 375, n2855. [Google Scholar] [CrossRef]
- Ledford, H. COVID antiviral pills: What scientists still want to know. Nature 2021, 599, 358–359. [Google Scholar] [CrossRef]
- Hariyanto, T.I.; Intan, D.; Hananto, J.E.; Harapan, H.; Kurniawan, A. Vitamin D supplementation and COVID-19 outcomes: A systematic review, meta-analysis and meta-regression. Rev. Med. Virol. 2021, e2269. [Google Scholar] [CrossRef]
- Thacher, T.D. Evaluating the Evidence in Clinical Studies of Vitamin D in COVID-19. Nutrients 2022, 14, 464. [Google Scholar] [CrossRef]
- Iacopetta, D.; Catalano, A.; Ceramella, J.; Saturnino, C.; Salvagno, L.; Ielo, I.; Drommi, D.; Scali, E.; Plutino, M.R.; Rosace, G.; et al. The different facets of triclocarban: A review. Molecules 2021, 26, 2811. [Google Scholar] [CrossRef]
- Mousavi-Roknabadi, R.S.; Arzhangzadeh, M.; Safaei-Firouzabadi, H.; Mousavi-Roknabadi, R.S.; Sharifi, M.; Fathi, N.; Jelyani, N.Z.; Mokdad, M. Methanol poisoning during COVID-19 pandemic; A systematic scoping review. Am. J. Emerg. Med. 2022, 52, 69–84. [Google Scholar] [CrossRef]
- Rizvi, S.G.; Ahammad, S.Z. COVID-19 and antimicrobial resistance: A cross-study. Sci. Total Environ. 2022, 807, 150873. [Google Scholar] [CrossRef]
- Catalano, A.; Iacopetta, D.; Ceramella, J.; Scumaci, D.; Giuzio, F.; Saturnino, C.; Aquaro, S.; Rosano, C.; Sinicropi, M.S. Multidrug resistance (MDR): A widespread phenomenon in pharmacological therapies. Molecules 2022, 27, 616. [Google Scholar] [CrossRef] [PubMed]
- Pozzi, C.; Ferrari, S.; Cortesi, D.; Luciani, R.; Stroud, R.M.; Catalano, A.; Costi, M.P.; Mangani, S. The structure of Enterococcus faecalis thymidylate synthase provides clues about folate bacterial metabolism. Acta Crystallogr. D Biol. Crystallogr. 2012, 68, 1232–1241. [Google Scholar] [CrossRef] [PubMed]
- Lascarrou, J.-B.; Colin, G.; Le Thuaut, A.; Serck, N.; Ohana, M.; Sauneuf, B.; Geri, G.; Mesland, J.-B.; Ribeyre, G.; Hussenet, C.; et al. Predictors of Negative First SARS-CoV-2 RT-PCR despite Final Diagnosis of COVID-19 and Association with Outcome. Sci. Rep. 2021, 11, 2388. [Google Scholar] [CrossRef] [PubMed]
- Jia, X.; Xiao, L.; Liu, Y. False negative RT-PCR and false positive antibody tests–concern and solutions in the diagnosis of COVID-19. J. Infect. 2021, 82, 414–451. [Google Scholar] [CrossRef]
- Aoki, K.; Takai, K.; Nagasawa, T.; Kashiwagi, K.; Mori, N.; Matsubayashi, K.; Satake, M.; Tanaka, I.; Kodama, N.; Shimodaira, T.; et al. Combination of a SARS-CoV-2 IgG assay and RT-PCR for improved COVID-19 diagnosis. Ann. Lab. Med. 2021, 41, 568–576. [Google Scholar] [CrossRef]
- Song, Y.; Zheng, S.; Li, L.; Zhang, X.; Zhang, X.; Huang, Z.; Chen, J.; Zhao, H.; Jie, Y.; Wang, R. Deep learning enables accurate diagnosis of novel coronavirus (COVID-19) with CT images. medRxiv 2020, 18, 2775–2780. [Google Scholar] [CrossRef]
- Chaudhary, P.K.; Pachori, R.B. FBSED based automatic diagnosis of COVID-19 using X-ray and CT images. Comput. Biol. Med. 2021, 134, 104454. [Google Scholar] [CrossRef]
- Chaqroun, A.; Hartard, C.; Schvoerer, E. Anti-SARS-CoV-2 vaccines and monoclonal antibodies facing viral variants. Viruses 2021, 13, 1171. [Google Scholar] [CrossRef]
- Mascola, J.R.; Graham, B.S.; Fauci, A.S. SARS-CoV-2 Viral Variants—Tackling a Moving Target. JAMA 2021, 325, 1261–1262. [Google Scholar] [CrossRef]
- Rambaut, A.; Holmes, E.C.; O’Toole, Á.; Hill, V.; McCrone, J.T.; Ruis, C.; du Plessis, L.; Pybus, O.G. A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nat. Microbiol. 2020, 5, 1403–1407. [Google Scholar] [CrossRef]
- Rambaut, A.; Holmes, E.C.; O’Toole, Á.; Hill, V.; McCrone, J.T.; Ruis, C.; du Plessis, L.; Pybus, O.G. Addendum: A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nat. Microbiol. 2021, 6, 415. [Google Scholar] [CrossRef] [PubMed]
- PANGO Lineages. Available online: https://cov-lineages.org (accessed on 1 February 2022).
- Shu, Y.; McCauley, J. GISAID: Global initiative on sharing all influenza data—From vision to reality. Eurosurveillance 2017, 22, 30494. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Clade and Lineage Nomenclature Aids in Genomic Epidemiology Studies of Active hCoV-19 Viruses. GISAID. Available online: https://go.nature.com/3pgSIt6 (accessed on 1 February 2022).
- Hadfield, J.; Megill, C.; Bell, S.M.; Huddleston, J.; Potter, B.; Callender, C.; Sagulenko, P.; Bedford, T.; Neher, R.A. Nextstrain: Real-time tracking of pathogen evolution. Bioinformatics 2018, 34, 4121–4123. [Google Scholar] [CrossRef] [PubMed]
- Bedford, T.; Hodcroft, E.B.; Neher, R.A. Updated Nextstrain SARS-CoV-2 Clade Naming Strategy. Nextstrain. Available online: https://go.nature.com/3c9Riep (accessed on 1 February 2022).
- WHO. COVID-19 Weekly Epidemiological Update—25 February 2021. Available online: https://go.nature.com/3uEtXIj (accessed on 1 February 2022).
- Chakraborty, C.; Bhattacharya, M.; Sharma, A.R. Present variants of concern and variants of interest of severe acute respiratory syndrome coronavirus 2: Their significant mutations in S-glycoprotein, infectivity, re-infectivity, immune escape and vaccines activity. Rev. Med. Virol. 2021, e2270. [Google Scholar] [CrossRef]
- Das, I. Vigilância genômica E. Monitoramento.; do, variantes. SARS-CoV-2. Available online: https://amazonia.fiocruz.br/wp-content/uploads/2021/09/Vigilancia_Genomica_do_SARS-CoV-2_no_Estado_do_Amazonas_No_02.pdf (accessed on 1 February 2022).
- Swift, C.L.; Isanovic, M.; Velez, K.E.C.; Norman, R.S. Community-level SARS-CoV-2 sequence diversity revealed by wastewater sampling. Sci. Total Environ. 2021, 801, 149691. [Google Scholar] [CrossRef]
- Focosi, D.; Tuccori, M.; Baj, A.; Maggi, F. SARS-CoV-2 variants: A synopsis of in vitro efficacy data of convalescent plasma, currently marketed vaccines, and monoclonal antibodies. Viruses 2021, 13, 1211. [Google Scholar] [CrossRef]
- Wahid, M.; Jawed, A.; Mandal, R.K.; Dailah, H.G.; Janahi, E.M.; Dhama, K.; Somvanshi, P.; Haque, S. Variants of SARS-CoV-2, their effects on infection, transmission and neutralization by vaccine induced antibodies. Eur. Rev. Med. Pharmacol. Sci. 2021, 25, 5857–5864. [Google Scholar]
- Dudas, G.; Hong, S.L.; Potter, B.I.; Calvignac-Spencer, S.; Niatou-Singa, F.S.; Tombolomako, T.B.; Fuh-Neba, T.; Vickos, U.; Ulrich, M.; Leendertz, F.H.; et al. Emergence and spread of SARS-CoV-2 lineage B. 1.620 with variant of concern-like mutations and deletions. Nat. Commun. 2021, 12, 5769. [Google Scholar] [CrossRef]
- Jhun, H.; Park, H.Y.; Hisham, Y.; Song, C.S.; Kim, S. SARS-CoV-2 Delta (B. 1.617. 2) variant: A unique T478K mutation in receptor binding motif (RBM) of spike gene. Immune Netw. 2021, 21, e32. [Google Scholar] [CrossRef]
- Regulatory Affairs Professionals Society COVID-19 Vaccine Tracker. Available online: https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker (accessed on 18 February 2022).
- Thomas, S.J.; Moreira, E.D., Jr.; 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 through 6 months. N. Engl. J. Med. 2021, 383, 2603–2615. [Google Scholar] [CrossRef]
- 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]
- Knoll, M.D.; Wonodi, C. Oxford-AstraZeneca COVID-19 vaccine efficacy. Lancet 2021, 397, 72–74. [Google Scholar] [CrossRef]
- Livingston, E.H.; Malani, P.N.; Creech, C.B. The Johnson & Johnson vaccine for COVID-19. JAMA 2021, 325, 1575. [Google Scholar] [PubMed]
- Miller, E. Rapid evaluation of the safety of COVID-19 vaccines: How well have we done? Clin. Microbiol. Infect. 2022; in press. [Google Scholar] [CrossRef] [PubMed]
- Klugar, M.; Riad, A.; Mekhemar, M.; Conrad, J.; Buchbender, M.; Howaldt, H.-P.; Attia, S. Side effects of mRNA-based and viral vector-based COVID-19 vaccines among german healthcare workers. Biology 2021, 10, 752. [Google Scholar] [CrossRef]
- Finsterer, J. Neurological side effects of SARS-CoV-2 vaccinations. Acta Neurol. Scand. 2022, 145, 5–9. [Google Scholar] [CrossRef] [PubMed]
- McMahon, D.E.; Kovarik, C.L.; Damsky, W.; Rosenbach, M.; Lipoff, J.B.; Tyagi, A.; Chamberlin, G.; Fathy, R.; Nazarian, R.M.; Desai, S.R.; et al. Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: A registry-based study. J. Am. Acad. Dermatol. 2022, 86, 113–121. [Google Scholar] [CrossRef] [PubMed]
- Mehta, H.; Handa, S.; Malhotra, P.; Patial, M.; Gupta, S.; Mukherjee, A.; Chatterjee, D.; Takkar, A.; Mahajan, R. Erythema nodosum, zoster duplex and pityriasis rosea as possible cutaneous adverse effects of Oxford–AstraZeneca COVID-19 vaccine: Report of three cases from India. J. Eur. Acad. Dermatol. Venereol. 2022, 36, e16–e18. [Google Scholar] [CrossRef]
- Iwanaga, J.; Fukuoka, H.; Fukuoka, N.; Yutori, H.; Ibaragi, S.; Tubbs, R.S. A narrative review and clinical anatomy of herpes zoster infection following COVID-19 vaccination. Clin. Anatom. 2022, 35, 45–51. [Google Scholar] [CrossRef]
- Koh, S.; Kim, H.N.; Kim, Y.S.; Kim, T.J. Varicella zoster virus reactivation in central and peripheral nervous systems following COVID-19 vaccination in an immunocompetent patient. J. Clin. Neurol. 2022, 18, 99–101. [Google Scholar] [CrossRef]
- Wei, N.; Kresch, M.; Elbogen, E.; Lebwohl, M. New onset and exacerbation of psoriasis after COVID-19 vaccination. JAAD Case Rep. 2022, 19, 74–77. [Google Scholar] [CrossRef] [PubMed]
- Poussaint, T.Y.; LaRovere, K.L.; Newburger, J.W.; Chou, J.; Nigrovic, L.E.; Novak, T.; Randolph, A.G. Multisystem Inflammatory-like Syndrome in a Child Following COVID-19 mRNA Vaccination. Vaccines 2022, 10, 43. [Google Scholar] [CrossRef] [PubMed]
- Stuart, A.S.; Shaw, R.H.; Liu, X.; Greenland, M.; Aley, P.K.; Andrews, N.J.; Cameron, J.C.; Charlton, S.; Clutterbuck, E.A.; Collins, A.M.; et al. Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): A single-blind, randomised, phase 2, non-inferiority trial. Lancet 2022, 399, 36–49. [Google Scholar] [CrossRef]
- Dolgin, E. Omicron is supercharging the COVID vaccine booster debate. Nature 2021, 10. [Google Scholar] [CrossRef] [PubMed]
- BIO, S. Status of COVID-19 Vaccines within WHO EUL/PQ Evaluation Process. Assessment. Status of COVID-19 Vaccines within WHO EUL/PQ Evaluation Process. 2021. Available online: https://extranet.who.int/pqweb/sites/default/files/documents/Status_COVID_VAX_29June2021.pdf (accessed on 28 February 2022).
- COVID-19 Vaccines WHO EUL issued|WHO—Prequalification of Medical Products (IVDs, Medicines, Vaccines and Immunization Devices, Vector Control). Available online: http://extranet.who.it/pqweb/ (accessed on 28 February 2022).
- Elekhnawy, E.; Kamar, A.A.; Sonbol, F. Present and future treatment strategies for coronavirus disease 2019. Fut. J. Pharm. Sci. 2021, 7, 1–9. [Google Scholar] [CrossRef]
- Peiris, S.; Mesa, H.; Aysola, A.; Manivel, J.; Toledo, J.; Borges-Sa, M.; Aldighieri, S.; Reveiz, L. Pathological findings in organs and tissues of patients with COVID-19: A systematic review. PLoS ONE 2021, 16, e0250708. [Google Scholar] [CrossRef]
- Cron, R.Q. COVID-19 cytokine storm: Targeting the appropriate cytokine. Lancet Rheumatol. 2021, 3, e236–e237. [Google Scholar] [CrossRef]
- Tarighi, P.; Eftekhari, S.; Chizari, M.; Sabernavaei, M.; Jafari, D.; Mirzabeigi, P. A review of potential suggested drugs for coronavirus disease (COVID-19) treatment. Eur. J. Pharmacol. 2021, 895, 173890. [Google Scholar] [CrossRef]
- Rubin, D.; Chan-Tack, K.; Farley, J.; Sherwat, A. FDA Approval of remdesivir—A Step in the Right Direction. N. Engl. J. Med. 2020, 383, 2598–2600. [Google Scholar] [CrossRef]
- Clerc, E.D. Remdesivir: Quo vadis? Biochem. Pharmacol. 2021, 193, 114800. [Google Scholar] [CrossRef]
- Liu, J.; Cao, R.; Xu, M.; Wang, X.; Zhang, H.; Hu, H.; Li, Y.; Hu, Z.; Zhong, W.; Wang, M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020, 6, 16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Horby, P.; Mafham, M.; Linsell, L.; Bell, J.L.; Staplin, N.; Emberson, J.R.; Wiselka, M.; Ustianowski, A.; Elmahi, E.; Prudon, B.; et al. Effect of hydroxychloroquine in hospitalized patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial. N. Engl. J. Med. 2020, 383, 2030–2040. [Google Scholar] [PubMed]
- Perez, J.; Roustit, M.; Lepelley, M.; Revol, B.; Cracowski, J.L.; Khouri, C. Reported adverse drug reactions associated with the use of hydroxychloroquine and chloroquine during the COVID-19 pandemic. Ann. Intern. Med. 2021, 74, 878–880. [Google Scholar] [CrossRef] [PubMed]
- Fuzimoto, A.D. An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment. J. Integr. Med. 2021, 19, 375–388. [Google Scholar] [CrossRef]
- Cao, R.; Hu, H.; Li, Y.; Wang, X.; Xu, M.; Liu, J.; Zhang, H.; Yan, Y.; Zhao, L.; Li, W.; et al. Anti-SARS-CoV-2 Potential of Artemisinins in vitro. ACS Infect. Dis. 2020, 6, 2524–2531. [Google Scholar] [CrossRef]
- Singh, A.K.; Singh, A.; Singh, R.; Misra, A. Molnupiravir in COVID-19: A systematic review of literature. Diabetes Metab. Syndr. Clin. Res. Rev. 2021, 15, 102329. [Google Scholar] [CrossRef]
- Heskin, J.; Pallett, S.J.; Mughal, N.; Davies, G.W.; Moore, L.S.; Rayment, M.; Jones, R. Caution required with use of ritonavir-boosted PF-07321332 in COVID-19 management. Lancet 2022, 399, 21–22. [Google Scholar] [CrossRef]
- U.S. Food and Drug Administration. Available online: https://www.fda.gov/media/138945/download (accessed on 28 February 2022).
- Echeverria-Esnal, D.; Martin-Ontiyuelo, C.; Navarrete-Rouco, M.E.; De-Antonio Cusco, M.; Ferrandez, O.; Horcajada, J.P.; Grau, S. Azithromycin in the treatment of COVID-19: A review. Expert Rev. Anti-Infect. 2021, 19, 147–163. [Google Scholar] [CrossRef]
- Chorin, E.; Dai, M.; Shulman, E.; Wadhwani, L.; Bar-Cohen, R.; Barbhayia, C.; Aizer, A.; Holmes, D.; Bernstein, S.; Spinelli, M.; et al. The QT interval in patients with SARS-CoV-2 infection treated with hydroxychloroquine/azithromycin. Nat. Med. 2020, 26, 808–809. [Google Scholar] [CrossRef]
- Montnach, J.; Baró, I.; Charpentier, F.; De Waard, M.; Loussouarn, G. Modelling sudden cardiac death risks factors in patients with coronavirus disease of 2019: The hydroxychloroquine and azithromycin case. Europace 2021, 23, 1124–1136. [Google Scholar] [CrossRef]
- Rosa, S.G.V.; Santos, W.C. Clinical trials on drug repositioning for COVID-19 treatment. Rev. Panam. Salud Pública 2020, 44, e40. [Google Scholar] [CrossRef] [PubMed]
- Iacopetta, D.; Carocci, A.; Sinicropi, M.S.; Catalano, A.; Lentini, G.; Ceramella, J.; Curcio, R.; Caroleo, M.C. Old drug scaffold, new activity: Thalidomide-correlated compounds exert different effects on breast cancer cell growth and progression. ChemMedChem 2017, 12, 381–389. [Google Scholar] [CrossRef] [PubMed]
- Zeinalian, M.; Salari-Jazi, A.; Jannesari, A.; Khanahmad, H. A potential protective role of losartan against coronavirus-induced lung damage. Infect. Control Hosp. Epidemiol. 2020, 41, 752–753. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tolouian, R.; Vahed, S.Z.; Ghiyasvand, S.; Tolouian, A.; Ardalan, M. COVID-19 interactions with angiotensin-converting enzyme 2 (ACE2) and the kinin system; looking at a potential treatment. J. Ren. Inj. Prev. 2020, 9, e19. [Google Scholar] [CrossRef]
- Chen, H.; Xie, J.; Su, N.; Wang, J.; Sun, Q.; Li, S.; Jin, J.; Zhou, J.; Mo, M.; Wei, Y.; et al. Corticosteroid therapy is associated with improved outcome in critically ill patients with COVID-19 with hyperinflammatory phenotype. Chest 2021, 159, 1793–1802. [Google Scholar] [CrossRef]
- Ranjbar, K.; Moghadami, M.; Mirahmadizadeh, A.; Fallahi, M.J.; Khaloo, V.; Shahriarirad, R.; Erfani, A.; Khodamoradi, Z.; Saadi, M.H.G. Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: A triple-blinded randomized controlled trial. BMC Infect. Dis. 2021, 21, 337. [Google Scholar] [CrossRef]
- Mukherjee, P.K.; Efferth, T.; Das, B.; Kar, A.; Ghosh, S.; Singha, S.; Debnath, P.; Sharma, N.; Bhardwaj, P.; Haldar, P.K. Role of medicinal plants in inhibiting SARS-CoV-2 and in the management of post-COVID-19 complications. Phytomedicine 2022, 98, 153930. [Google Scholar] [CrossRef]
- Lordan, R.; Rando, H.M.; Consortium, C.-R.; Greene, C.S. Dietary supplements and nutraceuticals under investigation for COVID-19 prevention and treatment. Msystems 2021, 6, e00122-21. [Google Scholar] [CrossRef]
- Baktash, V.; Hosack, T.; Patel, N.; Shah, S.; Kandiah, P.; Abbeele, K.V.D.; Mandal, A.K.J.; Missouris, C.G. Vitamin D status and outcomes for hospitalised older patients with COVID-19. Postgrad. Med. J. 2021, 97, 442–447. [Google Scholar] [CrossRef]
- Panfili, F.M.; Roversi, M.; D’Argenio, P.; Rossi, P.; Cappa, M.; Fintini, D. Possible role of vitamin D in COVID-19 infection in pediatric population. J. Endocrinol. Investig. 2020, 44, 27–35. [Google Scholar] [CrossRef]
- Zhang, J.; Rao, X.; Li, Y.; Zhu, Y.; Liu, F.; Guo, G.; Luo, G.; Meng, Z.; De Backer, D.; Xiang, H.; et al. Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann. Intensiv. Care 2021, 11, 5. [Google Scholar] [CrossRef] [PubMed]
- JamaliMoghadamSiahkali, S.; Zarezade, B.; Koolaji, S.; SeyedAlinaghi, S.; Zendehdel, A.; Tabarestani, M.; Moghadam, E.S.; Abbasian, L.; Manshadi, S.A.D.; Salehi, M. Safety and effectiveness of high-dose vitamin C in patients with COVID-19: A randomized open-label clinical trial. Eur. J. Med. Res. 2021, 26, 20. [Google Scholar] [CrossRef] [PubMed]
- Mhatre, S.; Srivastava, T.; Naik, S.; Patravale, V. Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: A review. Phytomedicine 2021, 85, 153286. [Google Scholar] [CrossRef] [PubMed]
- Derosa, G.; Maffioli, P.; D’Angelo, A.; Di Pierro, F. A role for quercetin in coronavirus disease 2019 (COVID-19). Phytother. Res. 2021, 35, 1230–1236. [Google Scholar] [CrossRef]
- Abdul-Hammed, M.; Adedotun, I.O.; Olajide, M.; Irabor, C.O.; Afolabi, T.I.; Gbadebo, I.O.; Rhymand, L.; Ramasami, P. Virtual screening, ADMET profiling, PASS prediction, and bioactivity studies of potential inhibitory roles of alkaloids, phytosterols, and flavonoids against COVID-19 main protease (Mpro). Nat. Prod. Res. 2021, 1–7. [Google Scholar] [CrossRef]
- Savant, S.; Srinivasan, S.; Kruthiventi, A.K. Potential Nutraceuticals for COVID-19. Nutr. Diet. Suppl. 2021, 13, 25. [Google Scholar] [CrossRef]
- Pastor, N.; Collado, M.C.; Manzoni, P. Phytonutrient and nutraceutical action against COVID-19: Current review of characteristics and benefits. Nutrients 2021, 13, 464. [Google Scholar] [CrossRef]
- Abian, O.; Ortega-Alarcon, D.; Jimenez-Alesanco, A.; Ceballos-Laita, L.; Vega, S.; Reyburn, H.T.; Rizzuti, B.; Velázquez-Campoy, A. Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening. Int. J. Biol. Macromol. 2020, 164, 1693–1703. [Google Scholar] [CrossRef]
- Vahedian-Azimi, A.; Abbasifard, M.; Rahimi-Bashar, F.; Guest, P.C.; Majeed, M.; Mohammadi, A.; Banach, M.; Jamialahmadi, T.; Sahebkar, A. Effectiveness of curcumin on outcomes of hospitalized COVID-19 patients: A systematic review of clinical trials. Nutrients 2022, 14, 256. [Google Scholar] [CrossRef]
- Serlahwaty, D.; Giovani, C. IAI CONFERENCE: In silico screening of mint leaves compound (Mentha piperita L.) as a potential inhibitor of SARS-CoV-2. Pharm. Educat. 2021, 21, 81–86. [Google Scholar] [CrossRef]
- Rosato, A.; Carocci, A.; Catalano, A.; Clodoveo, M.L.; Franchini, C.; Corbo, F.; Carbonara, G.G.; Carrieri, A.; Fracchiolla, G. Elucidation of the synergistic action of Mentha piperita essential oil with common antimicrobials. PLoS ONE 2018, 13, e0200902. [Google Scholar] [CrossRef] [PubMed]
- Yousefi, M.; Sadriirani, M.; PourMahmoudi, A.; Mahmoodi, S.; Samimi, B.; Hosseinikia, M.; Saeedinezhad, Z.; Panahande, S.B. Effects of pomegranate juice (Punica Granatum) on inflammatory biomarkers and complete blood count in patients with COVID-19: A structured summary of a study protocol for a randomized clinical trial. Trials 2021, 22, 246. [Google Scholar] [CrossRef] [PubMed]
- Fazio, A.; Iacopetta, D.; La Torre, C.; Ceramella, J.; Muia, N.; Catalano, A.; Carocci, A.; Sinicropi, M.S. Finding solutions for agricultural wastes: Antioxidant and antitumor properties of pomegranate Akko peel extracts and β-glucan recovery. Food Funct. 2018, 9, 6618–6631. [Google Scholar] [CrossRef] [PubMed]
- Singh, K.; Rao, A. Probiotics: A potential immunomodulator in COVID-19 infection management. Nutr. Res. 2021, 87, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Vlachou, M.; Siamidi, A.; Dedeloudi, A.; Konstantinidou, S.K.; Papanastasiou, I.P. Pineal hormone melatonin as an adjuvant treatment for COVID-19. Int. J. Mol. Med. 2021, 47, 1. [Google Scholar] [CrossRef]
- Camp, O.G.; Bai, D.; Gonullu, D.C.; Nayak, N.; Abu-Soud, H.M. Melatonin interferes with COVID-19 at several distinct ROS-related steps. J. Inorg. Biochem. 2021, 223, 111546. [Google Scholar] [CrossRef]
- Khoramipour, K.; Basereh, A.; Hekmatikar, A.A.; Castell, L.; Ruhee, R.T.; Suzuki, K. Physical activity and nutrition guidelines to help with the fight against COVID-19. J. Sports Sci. 2021, 39, 101–107. [Google Scholar] [CrossRef]
- Ransing, R.; da Costa, M.P.; Adiukwu, F.; Grandinetti, P.; Teixeira, A.L.S.; Kilic, O.; Soler-Vidal, J.; Ramalho, R. Yoga for COVID-19 and natural disaster related mental health issues: Challenges and perspectives. Asian J. Psych. 2020, 53, 102386. [Google Scholar] [CrossRef]
- Leustean, L.; Preda, C.; Teodoriu, L.; Mihalache, L.; Arhire, L.; Ungureanu, M.C. Role of irisin in endocrine and metabolic disorders—Possible new therapeutic agent? Appl. Sci. 2021, 11, 5579. [Google Scholar] [CrossRef]
- Catalano, A. COVID-19: Could irisin become the handyman myokine of the 21st century. Coronaviruses 2020, 1, 32–41. [Google Scholar] [CrossRef]
- De Oliveira, M.; De Sibio, M.T.; Mathias, L.S.; Rodrigues, B.M.; Sakalem, M.E.; Nogueira, C.R. Irisin modulates genes associated with severe coronavirus disease (COVID-19) outcome in human subcutaneous adipocytes cell culture. Mol. Cell. Endocrinol. 2020, 515, 110917. [Google Scholar] [CrossRef] [PubMed]
- De Loera, D. The role of traditional medicine in the fight against SARS-CoV-2. In Biomedical Innovations to Combat COVID-19; Academic Press: Cambridge, MA, USA, 2022; pp. 339–385. [Google Scholar]
- Dotolo, S.; Marabotti, A.; Facchiano, A.; Tagliaferri, R. A review on drug repurposing applicable to COVID-19. Brief. Bioinform. 2020, 22, 726–741. [Google Scholar] [CrossRef] [PubMed]
- Sharma, D.; Kunamneni, A. Recent progress in the repurposing of drugs/molecules for the management of COVID-19. Exp. Rev. Anti-Infect. Ther. 2021, 19, 889–897. [Google Scholar] [CrossRef] [PubMed]
- Asrani, P.; Tiwari, K.; Eapen, M.S.; McAlinden, K.D.; Haug, G.; Johansen, M.D.; Hansbro, P.M.; Flanagan, K.N.; Hassan, M.I.; Sohal, S.S. Clinical features and mechanistic insights into drug repurposing for combating COVID-19. Int. J. Biochem. Cell Biol. 2022, 142, 106114. [Google Scholar] [CrossRef] [PubMed]
- Gao, K.; Nguyen, D.D.; Chen, J.; Wang, R.; Wei, G.W. Repositioning of 8565 existing drugs for COVID-19. J. Phys. Chem. Lett. 2020, 11, 5373–5382. [Google Scholar] [CrossRef]
- Nejadi Babadaei, M.M.; Hasan, A.; Vahdani, Y.; Haj Bloukh, S.; Sharifi, M.; Kachooei, E.; Haghighat, S.; Falahati, M. Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase. J. Biomol. Struct. Dyn. 2021, 39, 3771–3779. [Google Scholar] [CrossRef]
- Bibi, N.; Farid, A.; Gul, S.; Ali, J.; Amin, F.; Kalthiya, U.; Hupp, T. Drug repositioning against COVID-19: A first line treatment. J. Biomol. Struct. Dyn. 2021, 1–15. [Google Scholar] [CrossRef]
- Ge, Y.; Tian, T.; Huang, S.; Wan, F.; Li, J.; Li, S.; Wang, X.; Yang, H.; Hong, L.; Wu, N.; et al. An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19. Signal. Transduct. Target. Ther. 2021, 6, 165. [Google Scholar] [CrossRef]
- Serafin, M.B.; Bottega, A.; Foletto, V.S.; da Rosa, T.F.; Horner, A.; Horner, R. Drug repositioning is an alternative for the treatment of coronavirus COVID-19. Int. J. Antimicrob. Agents 2020, 55, 105969. [Google Scholar] [CrossRef]
- Low, Z.Y.; Yip, A.J.W.; Lal, S.K. Repositioning Ivermectin for COVID-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication. Biochim. Biophys. Acta 2022, 1868, 166294. [Google Scholar] [CrossRef]
- Catalano, A.; Iacopetta, D.; Pellegrino, M.; Aquaro, S.; Franchini, C.; Sinicropi, M.S. Diarylureas: Repositioning from antitumor to antimicrobials or multi-target agents against new pandemics. Antibiotics 2021, 10, 92. [Google Scholar] [CrossRef] [PubMed]
- Catalano, A.; Iacopetta, D.; Sinicropi, M.S.; Franchini, C. Diarylureas as antitumor agents. Appl. Sci. 2021, 11, 374. [Google Scholar] [CrossRef]
- Iacopetta, D.; Ceramella, J.; Catalano, A.; Saturnino, C.; Bonomo, M.G.; Franchini, C.; Sinicropi, M.S. Schiff bases: Interesting scaffolds with promising antitumoral properties. Appl. Sci. 2021, 11, 1877. [Google Scholar] [CrossRef]
- Mansour, M.A.; AboulMagd, A.M.; Abdel-Rahman, H.M. Quinazoline-Schiff base conjugates: In silico study and ADMET predictions as multi-target inhibitors of coronavirus (SARS-CoV-2) proteins. RSC Adv. 2020, 10, 34033–34045. [Google Scholar] [CrossRef]
- Ceramella, J.; Iacopetta, D.; Catalano, A.; Cirillo, F.; Lappano, R.; Sinicropi, M.S. A review on the antimicrobial activity of schiff bases: Data collection and recent studies. Antibiotics 2022, 11, 191. [Google Scholar] [CrossRef]
- El-Gammal, O.A.; El-Bindary, A.A.; Mohamed, F.S.; Rezk, G.N.; El-Bindary, M.A. Synthesis, characterization, design, molecular docking, anti COVID-19 activity, DFT calculations of novel Schiff base with some transition metal complexes. J. Mol. Liq. 2021, 346, 117850. [Google Scholar] [CrossRef]
- Catalano, A.; Sinicropi, M.S.; Iacopetta, D.; Ceramella, J.; Mariconda, A.; Rosano, C.; Scali, E.; Saturnino, C.; Longo, P. A review on the advancements in the field of metal complexes with Schiff bases as antiproliferative agents. Appl. Sci. 2021, 11, 6027. [Google Scholar] [CrossRef]
- Goris, T.; Perez-Valero, A.; Martınez, I.; Dong, Y.; Fernandez-Calleja, L.; San Leon, D.; Bornscheuer, U.T.; Magadan-Corpas, P.; Lombo, F.; Nogales, J. Repositioning microbial biotechnology against COVID-19: The case of microbial production of flavonoids. Microb. Biotechnol. 2021, 14, 94–110. [Google Scholar] [CrossRef]
- Szendrey, M.; Guo, J.; Li, W.; Yang, T.; Zhang, S. COVID-19 drugs chloroquine and hydroxychloroquine, but not azithromycin and remdesivir, block hERG potassium channels. J. Pharmacol. Exp. Ther. 2021, 377, 265–272. [Google Scholar] [CrossRef]
- Bruno, C.; Carocci, A.; Catalano, A.; Cavalluzzi, M.M.; Corbo, F.; Franchini, C.; Lentini, G.; Tortorella, V. Facile, alternative route to lubeluzole, its enantiomer, and the racemate. Chirality 2006, 18, 227–231. [Google Scholar] [CrossRef]
- Gualdani, R.; Cavalluzzi, M.M.; Tadini-Buoninsegni, F.; Convertino, M.; Gailly, P.; Stary-Weinzinger, A.; Lentini, G. Molecular insights into hERG potassium channel blockade by lubeluzole. Cell. Physiol. Biochem. 2018, 45, 2233–2245. [Google Scholar] [CrossRef] [PubMed]
- Alonzi, T.; Aiello, A.; Petrone, L.; Najafi Fard, S.; D’eletto, M.; Falasca, L.; Nardacci, R.; Rossin, F.; Delogu, C.; Castilletti, C.; et al. Cysteamine with in vitro antiviral activity and immunomodulatory effects has the potential to be a repurposing drug candidate for COVID-19 therapy. Cells 2022, 11, 52. [Google Scholar] [CrossRef] [PubMed]
- Vangeel, L.; De Jonghe, S.; Maes, P.; Slechten, B.; Raymenants, J.; André, E.; Neyts, J.; Jochmans, D. Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antivir. Res. 2022, 198, 105252. [Google Scholar] [CrossRef] [PubMed]
- Rai, D.K.; Yurgelonis, I.; McMonagle, P.; Rothan, H.A.; Hao, L.; Gribenko, A.; Titova, E.; Kreiswirth, B.; White, K.M.; Zhu, Y.; et al. Nirmatrelvir, an orally active Mpro inhibitor, is a potent inhibitor of SARS-CoV-2 Variants of Concern. bioRxiv 2022. [Google Scholar] [CrossRef]
- Rosales, R.; McGovern, B.L.; Rodriquez, M.L.; Rai, D.K.; Cardin, R.D.; Anderson, A.S.; PSP Study Group; Sordillo, E.M.; van Bakel, H.; Simon, V.; et al. Nirmatrelvir, molnupiravir, and remdesivir maintain potent in vitro activity against the SARS-CoV-2 Omicron variant. bioRxiv 2022. [Google Scholar] [CrossRef]
- Yadav, P.D.; Gupta, N.; Potdar, V.; Mohandas, S.; Sahay, R.R.; Sarkale, P.; Shete, A.M.; Razdan, A.; Patil, D.Y.; Nyayanit, D.A.; et al. An in vitro and in vivo approach for the isolation of Omicron variant from human clinical specimens. bioRxiv 2022. [Google Scholar] [CrossRef]
- Touret, F.; Baronti, C.; Bouzidi, H.S.; de Lamballerie, X. In vitro evaluation of therapeutic antibodies against a SARS-CoV-2 Omicron, B. 1.1. 529 isolate. bioRxiv 2022. [Google Scholar] [CrossRef]
- Liesenborghs, L.; Spriet, I.; Jochmans, D.; Belmans, A.; Gyselinck, I.; Teuwen, L.-A.; ter Horst, S.; Dreesen, E.; Geukens, T.; Engelen, M.M.; et al. Itraconazole for COVID-19: Preclinical studies and a proof-of-concept randomized clinical trial. EBioMedicine 2021, 66, 103288. [Google Scholar] [CrossRef]
- Frumkin, L.R.; Lucas, M.; Scribner, C.L.; Ortega-Heinly, N.; Rogers, J.; Yin, G.; Hallam, T.J.; Yam, A.; Bedard, K.; Begley, R.; et al. Egg-derived anti-SARS-CoV-2 immunoglobulin Y (IgY) with broad variant activity as intranasal prophylaxis against COVID-19: Preclinical studies and randomized controlled phase 1 clinical trial. medRxiv 2022. [Google Scholar] [CrossRef]
- Raghavan, K.; Dedeepiya, V.D.; Suryaprakash, V.; Rao, K.S.; Ikewaki, N.; Sonoda, T.; Levy, G.A.; Iwasaki, M.; Senthilkumar, R.; Preethy, S.; et al. Beneficial effects of novel Aureobasidium pullulans strains produced Beta-1,3-1,6 Glucans on Interleukin-6 and D-Dimer levels in COVID-19 patients; results of a randomized multiple-arm pilot clinical study. Biomed. Pharmacother. 2022, 145, 112243. [Google Scholar] [CrossRef]
- Elamir, Y.M.; Amir, H.; Lim, S.; Rana, Y.P.; Lopez, C.G.; Feliciano, N.V.; Omar, A.; Grist, W.P.; Via, M.A. A randomized pilot study using calcitriol in hospitalized COVID-19 patients. Bone 2021, 154, 116175. [Google Scholar] [CrossRef] [PubMed]
- Buonfrate, D.; Chesini, F.; Martini, D.; Roncaglioni, M.C.; Fernandez, M.L.O.; Alvisi, M.F.; De Simone, I.; Rulli, E.; Nobili, A.; Casalini, G.; et al. High dose ivermectin for the early treatment of COVID-19 (COVER study): A randomised, double-blind, multicentre, phase II, dose-finding, proof of concept clinical trial. Int. J. Antimicrob. Agents 2022, 59, 106516. [Google Scholar] [CrossRef] [PubMed]
Variant Name (Pango Lineage) | GISAID Database | Nextstrain Database | WHO Names | Variant Name (Pango Sublineage) | WHO Designation | Date of Designation | |
---|---|---|---|---|---|---|---|
B.1.525 | G/484K.V3 | 20A/S:484K | Eta | η | – | VOI | UK/Nigeria December 2020 |
B.1.526 | GH | 20C/S:484K | Iota | ι | – | VOI | New York, NY, (USA) November 2020 |
– | – | 20C | – | – | B.1.526.1 | VOI | USA October 2020 |
B.1.617 | G/452R.V3 | 20A | |||||
20A/S:154K | Kappa | κ | B.1.617.1 | VOI | India December 2020 | ||
– | G/452R.V3 | 20A/S:478K | Delta | δ | B.1.617.2 | VOC | India October 2020 |
– | – | 20A | – | – | B.1.617.3 | VOI | India October 2020 |
C.37 | – | – | Lambda | λ | – | VOI | Lima November 2020 |
B.1.621 | – | – | Mu | μ | – | VOI | Colombia January 2021 |
P.2 | GR | 20B/S:484K | Zeta | ζ | B.1.1.28.2 | VOI | Rio de Janeiro (Brazil) April 2020 |
P.3 | GR | 20B/S:265C | Theta | θ | B.1.1.28.3 | VOI | Japan/Philippines, January 2021 |
B.1.616 | – | 20C | – | – | – | VOI | France January 2021 |
B1.1.7 | GRY (formerly GR/501Y.V1) | 20I/S:501Y.V1 | Alpha | α | – | VOC | South-East England (UK), September 2020 |
B1.351 | GH/501Y.V2 | 20H/501Y.V2 | Beta | β | – | VOC | South Africa, May 2020 |
P.1 | GR/501Y.V3 | 20J/S:501Y.V3 | Gamma | γ | B.1.1.28.1 or P.1 | VOC | Japan/Amazonas (Brazil), November 2020 |
B.1.427 | GH/452R.V1 | 20C/S:452R | Epsilon | ε | – | VOI a | Southern California (USA) December 2020 |
B.1.429 | GH/452R.V1 | 20C/S:452R | Formerly Epsilon | Formerly ε | – | VOI a | Southern California, CA, (USA) |
B.1.620 | – | – | – | – | B1.177 | VOC | Lithuania April 2021 |
– | – | – | – | B.1.258D | Other | Czech Republic/Slovakia | |
– | – | – | – | B.1.1.298 | Other | Denmark | |
BA.1/BA.2 | – | – | Omicron | o | B.1.1.529 | VOC | South Africa (early Nov. 2021) |
Manufacturer/WHO EUL Holder | Name of Vaccine | Platform | NRA of Record | Recommendation Issued |
---|---|---|---|---|
Pfizer Biontech | BNT162b2/COMIRNATY® Tozinameran (INN) | Nucleoside modified mRNA | EMA FDA | 31 December 20 16 July 21 |
Astra Zeneca | AZD1222 VAXZEVRIA | Recombinant ChAdOx1 adenoviral vector encoding the Spike protein antigen of the SARS-CoV-2 | EMA MFDS KOREA Japan MHLW PMDA Australian TGA | 15 April 21 15 February 21 9 July 21 |
Serum Institute of India | CovishieldTM (ChAdOx1_nCoV-19) | Recombinant ChAdOx1 adenoviral vector encoding the Spike protein antigen of the SARS-CoV-2 | DCGI | 15 February 21 |
Janssen | Ad26.COV2.S | Recombinant, replication-incompetent adenovirus type 26 (Ad26) vectored vaccine encoding the SARS-CoV-2 Spike (S) protein | EMA | 12 March 21 |
Moderna | mRNA-1273 SPIKEVAX | mRNA-based vaccine encapsulated in lipid nanoparticle (LNP) | EMA MFDS FDA | 30 April 21 23 December 21 6 August 21 |
Sinopharm (Beijing, Wuhan)/BIBP | SARS-CoV-2 Vaccine (Vero Cell), Inactivated (lnCoV) | Inactivated, produced in Vero cells | NMPA | 7 May 21 |
Sinovac | SARS-CoV-2 Vaccine (Vero Cell), Inactivated (lnCoV) CoronaVac | Inactivated, produced in Vero cells | NMPA | 1 June 21 |
The Gamaleya National Center of Epidemiology and Microbiology | Sputnik V | Human adenovirus vector-based COVID-19 vaccine | Russian NRA | 11 August 20 |
CanSinoBIO- Beijing Institute of Biotechnology | Ad5-nCoV | Inactivated, produced in Vero cells | NMPA | – |
Bharat Biotech, India | SARS-CoV-2 Vaccine, Inactivated (Vero Cell)/COVAXIN® | Whole-virion inactivated Vero cell | DCGI/CDSCO | 3 November 21 |
Novavax | NVX-CoV2373/Covovax NUVAXOVID™ | Recombinant nanoparticle prefusion spike protein formulated with Matrix-M™ adjuvant | EMA | 21 December 21 |
CureVac | Zorecimeran (INN) concentrate and solvent for dispersion for injection; Company code: CVnCoV/CV07050101 | mRNA-based vaccine encapsulated in lipid nanoparticle (LNP) | EMA | – |
Sanofi Pasteur | CoV2 preS dTM-AS03 vaccine | Recombinant, adjuvanted | EMA | – |
Structure | Name | Class | Ref. |
---|---|---|---|
Remdesivir | Antiviral Nucleoside analogue | [81,82] | |
Chroloquine | Antimalarial | [83,84,85] | |
Hydroxychloroquine | Antimalarial | [83,84,85] | |
Artesunate | Antimalarial | [86,87] | |
Arteannuin B | Antimalarial | [86,87] | |
Lumefantrine | Antimalarial | [86,87] | |
Molnupiravir | Antiviral Nucleoside analogue | [27,88] | |
Paxlovid (ritonavir + nirmatrelvir) | Antiviral Viral protease inhibitor | [89] | |
Azithromycin | Antimicrobial | [91] | |
Mexiletine | Antiarrhythmic | [92,93] | |
Monoclonal antibody | Bevacizumab | Angiogenesis inhibitor | [94] |
Thalidomide | Immunomodulator | [95] | |
Losartan | Angiotensin II receptor blockers | [96] | |
Icatibant | Bradykinin B2 receptor antagonist | [97] | |
Methylprednisolone | Corticosteroid | [98,99] | |
Dexamethasone | Corticosteroid | [98,99] |
Type of Clinical Studies | Treatments | Participants | Administration | Results |
---|---|---|---|---|
Double-blind, randomized, placebo-controlled phase 1 study | Chicken egg yolk-derived anti-index SARS- CoV-2 RBD IgY polyclonal antibodies as an intranasal drop product | 48 healthy adults | Intranasally single-ascending doses of 2, 4, and 8 mg for 14 days | Excellent safety and tolerability profile and absence of systemic absorption |
Randomized multiple-arm pilot clinical study | Beta glucans derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans | 24 RT-PCR positive COVID-19 patients | Additional supplementation for 30 days Group 1 control Group 2: AFO-202 beta glucan Group 3: a combination of AFO-202 and N-163 beta glucans | Significant control of IL6, D-Dimer and NLR, a significant increase in LCR, LeCR and marginal control of ESR in COVID-19 patients |
Open label, randomized clinical trial | Calcitriol for the treatment of COVID-19 | 50 patients hospitalized with COVID-19 | 0.5 μg daily for 14 days | Improvement in oxygenation among hospitalized |
Randomized, double-blind, multicenter, phase II, dose-finding, proof-of-concept clinical trial | Ivermectin for the treatment of COVID-19 | 89 adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection | (A) placebo (B) single-dose 600 μg/kg plus placebo for 5 days (C) single-dose 1200 μg/kg for 5 days | No significant reduction in viral load between ivermectin and placebo groups |
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Iacopetta, D.; Ceramella, J.; Catalano, A.; Saturnino, C.; Pellegrino, M.; Mariconda, A.; Longo, P.; Sinicropi, M.S.; Aquaro, S. COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies. Viruses 2022, 14, 573. https://doi.org/10.3390/v14030573
Iacopetta D, Ceramella J, Catalano A, Saturnino C, Pellegrino M, Mariconda A, Longo P, Sinicropi MS, Aquaro S. COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies. Viruses. 2022; 14(3):573. https://doi.org/10.3390/v14030573
Chicago/Turabian StyleIacopetta, Domenico, Jessica Ceramella, Alessia Catalano, Carmela Saturnino, Michele Pellegrino, Annaluisa Mariconda, Pasquale Longo, Maria Stefania Sinicropi, and Stefano Aquaro. 2022. "COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies" Viruses 14, no. 3: 573. https://doi.org/10.3390/v14030573
APA StyleIacopetta, D., Ceramella, J., Catalano, A., Saturnino, C., Pellegrino, M., Mariconda, A., Longo, P., Sinicropi, M. S., & Aquaro, S. (2022). COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies. Viruses, 14(3), 573. https://doi.org/10.3390/v14030573