Special Issue "Vaccines and Therapeutics against Coronaviruses"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: 31 August 2021.

Special Issue Editors

Dr. Kenneth Lundstrom
E-Mail Website
Guest Editor
PanTherapeutics, Rue des Remparts 4, CH1095 Lutry, Switzerland
Interests: viral gene therapy; viral vaccines; gene expression using viral vectors; structural biology; epigenetics; nutrigenomics
Special Issues and Collections in MDPI journals
Dr. Alaa A. A. Aljabali
E-Mail Website
Guest Editor
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid 21163, P. O. BOX 566, Jordan
Interests: viruses; virus-like particles (VLPs); chemical engineering; biological nanoparticles; immune therapy

Special Issue Information

Dear Colleagues,

The current COVID-19 pandemic has caused unprecedented devastation to health and the economy around the world, and is expected to continue for an unforeseen time into the future due to the lack of existing antiviral drugs and vaccines. In a unique cooperation between academic institutions, pharmaceutical and biotech enterprises, and governmental organizations, the research and development of vaccines and therapeutics against COVID-19 is occurring at a level never seen before. This research has generated plenty of new information on COVID-19 as well as SARS-CoV-2, responsible for the pandemic, as illustrated by the 74,417 publications found in PubMed when using the search term “COVID-19”. Today, some drugs have demonstrated specific efficacy in the treatment of seriously ill COVID-19 patients, and two vaccine candidates have shown promising primary results in phase III clinical trials. However, we have not yet conquered the disease, and research and development on vaccines and therapeutics should continue at maximum speed and effort. Therefore, it is time to welcome contributions to this Special Issue of Viruses, “Vaccines and Therapeutics against Coronaviruses”. The aim is to provide comprehensive information on all aspects of coronavirus research and development on vaccines and therapeutics. To achieve this goal, it is essential to understand the biology and virology of coronaviruses. Application of bioinformatics, mathematics, genomics, structural biology, and modeling is an essential part of developing safe and efficient vaccines and therapeutics. We also need to develop the best tools and strategies possible for vaccine and drug delivery systems. Epidemiology and diagnostics are also important areas to discuss. Finally, another aim is to outline the strategy for confronting future emerging outbreaks caused by coronaviruses or some other novel virus. We cordially invite you to contribute to the Special Issue “Vaccines and Therapeutics against Coronaviruses” to advance our knowledge on coronaviruses and to discover the means to overcome the pandemic together.

Dr. Kenneth Lundstrom
Dr. Alaa A. A. Aljabali
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SARS-CoV-2
  • COVID-19
  • antivirals
  • vaccines
  • therapeutics

Related Special Issue

Published Papers (18 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

Article
Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon
Viruses 2021, 13(6), 989; https://doi.org/10.3390/v13060989 - 26 May 2021
Viewed by 2707
Abstract
Objective: This study was designed to determine the efficacy of ivermectin, an FDA-approved drug, in producing clinical benefits and decreasing the viral load of SARS-CoV-2 among asymptomatic subjects that tested positive for this virus in Lebanon. Methods: A randomized controlled trial was conducted [...] Read more.
Objective: This study was designed to determine the efficacy of ivermectin, an FDA-approved drug, in producing clinical benefits and decreasing the viral load of SARS-CoV-2 among asymptomatic subjects that tested positive for this virus in Lebanon. Methods: A randomized controlled trial was conducted in 100 asymptomatic Lebanese subjects that have tested positive for SARS-CoV2. Fifty patients received standard preventive treatment, mainly supplements, and the experimental group received a single dose (according to body weight) of ivermectin, in addition to the same supplements the control group received. Results: There was no significant difference (p = 0.06) between Ct-values of the two groups before the regimen was started (day zero), indicating that subjects in both groups had similar viral loads. At 72 h after the regimen started, the increase in Ct-values was dramatically higher in the ivermectin than in the control group. In the ivermectin group, Ct increased from 15.13 ± 2.07 (day zero) to 30.14 ± 6.22 (day three; mean ± SD), compared to the control group, where the Ct values increased only from 14.20 ± 2.48 (day zero) to 18.96 ± 3.26 (day three; mean ± SD). Moreover, more subjects in the control group developed clinical symptoms. Three individuals (6%) required hospitalization, compared to the ivermectin group (0%). Conclusion: Ivermectin appears to be efficacious in providing clinical benefits in a randomized treatment of asymptomatic SARS-CoV-2-positive subjects, effectively resulting in fewer symptoms, lower viral load and reduced hospital admissions. However, larger-scale trials are warranted for this conclusion to be further cemented. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Article
Exploring the Role of Glycans in the Interaction of SARS-CoV-2 RBD and Human Receptor ACE2
Viruses 2021, 13(5), 927; https://doi.org/10.3390/v13050927 - 17 May 2021
Viewed by 829
Abstract
COVID-19 is a highly infectious respiratory disease caused by the novel coronavirus SARS-CoV-2. It has become a global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, the Spike RBD of SARS-CoV-2 binds the human host cell [...] Read more.
COVID-19 is a highly infectious respiratory disease caused by the novel coronavirus SARS-CoV-2. It has become a global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, the Spike RBD of SARS-CoV-2 binds the human host cell receptor ACE2, enabling the virus to enter the host cell. Both the Spike and ACE2 are densely glycosylated, and it is unclear how distinctive glycan types may modulate the interaction of RBD and ACE2. Detailed understanding of these determinants is key for the development of novel therapeutic strategies. To this end, we perform extensive all-atom simulations of the (i) RBD-ACE2 complex without glycans, (ii) RBD-ACE2 with oligomannose MAN9 glycans in ACE2, and (iii) RBD-ACE2 with complex FA2 glycans in ACE2. These simulations identify the key residues at the RBD-ACE2 interface that form contacts with higher probabilities, thus providing a quantitative evaluation that complements recent structural studies. Notably, we find that this RBD-ACE2 contact signature is not altered by the presence of different glycoforms, suggesting that RBD-ACE2 interaction is robust. Applying our simulated results, we illustrate how the recently prevalent N501Y mutation may alter specific interactions with host ACE2 that facilitate the virus-host binding. Furthermore, our simulations reveal how the glycan on Asn90 of ACE2 can play a distinct role in the binding and unbinding of RBD. Finally, an energetics analysis shows that MAN9 glycans on ACE2 decrease RBD-ACE2 affinity, while FA2 glycans lead to enhanced binding of the complex. Together, our results provide a more comprehensive picture of the detailed interplay between virus and human receptor, which is much needed for the discovery of effective treatments that aim at modulating the physical-chemical properties of this virus. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Article
Screening of FDA-Approved Drugs Using a MERS-CoV Clinical Isolate from South Korea Identifies Potential Therapeutic Options for COVID-19
Viruses 2021, 13(4), 651; https://doi.org/10.3390/v13040651 - 09 Apr 2021
Cited by 2 | Viewed by 661
Abstract
Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 [...] Read more.
Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6, representing effective drugs. The time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs which acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI > 100), atovaquone, an anti-malarial (TI > 34), and ciclesonide, an inhalable corticosteroid (TI > 6). Furthermore, utilizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we tested combinations of remdesivir with selected drugs in Vero-E6 and Calu-3 cells, in lung organoids, and identified ciclesonide, nelfinavir, and camostat to be at least additive in vitro. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Article
Glycyrrhizin Effectively Inhibits SARS-CoV-2 Replication by Inhibiting the Viral Main Protease
Viruses 2021, 13(4), 609; https://doi.org/10.3390/v13040609 - 02 Apr 2021
Cited by 6 | Viewed by 1686
Abstract
The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected people are still limited. Clearly, novel antiviral compounds for the treatment of SARS-CoV-2 infected patients are [...] Read more.
The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected people are still limited. Clearly, novel antiviral compounds for the treatment of SARS-CoV-2 infected patients are still urgently needed. Complementary medicine is used along with standard medical treatment and accessible to a vast majority of people worldwide. Natural products with antiviral activity may contribute to improve the overall condition of SARS-CoV-2 infected individuals. In the present study, we investigated the antiviral activity of glycyrrhizin, the primary active ingredient of the licorice root, against SARS-CoV-2. We demonstrated that glycyrrhizin potently inhibits SARS-CoV-2 replication in vitro. Furthermore, we uncovered the underlying mechanism and showed that glycyrrhizin blocks the viral replication by inhibiting the viral main protease Mpro that is essential for viral replication. Our data indicate that the consumption of glycyrrhizin-containing products such as licorice root tea of black licorice may be of great benefit for SARS-CoV-2 infected people. Furthermore, glycyrrhizin is a good candidate for further investigation for clinical use to treat COVID-19 patients. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Article
In Vitro Assessment of the Antiviral Activity of Ketotifen, Indomethacin and Naproxen, Alone and in Combination, against SARS-CoV-2
Viruses 2021, 13(4), 558; https://doi.org/10.3390/v13040558 - 26 Mar 2021
Viewed by 1669
Abstract
The 2019 coronavirus infectious disease (COVID-19) is caused by infection with the new severe acute respiratory syndrome coronavirus (SARS-CoV-2). Currently, the treatment options for COVID-19 are limited. The purpose of the experiments presented here was to investigate the effectiveness of ketotifen, naproxen and [...] Read more.
The 2019 coronavirus infectious disease (COVID-19) is caused by infection with the new severe acute respiratory syndrome coronavirus (SARS-CoV-2). Currently, the treatment options for COVID-19 are limited. The purpose of the experiments presented here was to investigate the effectiveness of ketotifen, naproxen and indomethacin, alone or in combination, in reducing SARS-CoV-2 replication. In addition, the cytotoxicity of the drugs was evaluated. The findings showed that the combination of ketotifen with indomethacin (SJP-002C) or naproxen both reduce viral yield. Compared to ketotifen alone (60% inhibition at EC50), an increase in percentage inhibition of SARS-CoV-2 to 79%, 83% and 93% was found when co-administered with 25, 50 and 100 μM indomethacin, respectively. Compared to ketotifen alone, an increase in percentage inhibition of SARS-CoV-2 to 68%, 68% and 92% was found when co-administered with 25, 50 and 100 μM naproxen, respectively. For both drug combinations the observations suggest an additive or synergistic effect, compared to administering the drugs alone. No cytotoxic effects were observed for the administered dosages of ketotifen, naproxen, and indomethacin. Further research is warranted to investigate the efficacy of the combination of ketotifen with indomethacin (SJP-002C) or naproxen in the treatment of SARS-CoV-2 infection in humans. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Article
Treatment Protocol for COVID-19 Based on T2R Phenotype
Viruses 2021, 13(3), 503; https://doi.org/10.3390/v13030503 - 18 Mar 2021
Viewed by 1058
Abstract
COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on [...] Read more.
COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on this, we proposed assessing the different T2R38 phenotypes response towards a targeted treatment protocol. Starting July 2020 till December 2020, we tested subjects for T2R38 phenotypic expression (supertasters, tasters, and nontasters). Subjects who were subsequently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (diagnosed via PCR) were included. Based on their taster status, supertasters were given dexamethasone for 4 days; tasters were given azithromycin and dexamethasone +/− hydroxychloroquine for 7 days; and nontasters were given azithromycin and dexamethasone for 12 days. Subjects were followed prospectively and their outcomes were documented. Seven hundred forty-seven COVID-19 patients were included, with 184 (24.7%) supertasters, 371 (49.6%) tasters, and192 (25.7%) nontasters. The average duration of symptoms with the treatment protocol was 5 days for supertasters, 8.1 days for tasters, and 16.2 days for nontasters. Only three subjects (0.4%) required hospitalization (3/3 nontasters). Targeted treatment protocol showed significant correlation (p < 0.05) based on patients’ T2R38 phenotypic expression. Assessing treatment protocols for COVID-19 patients according to their T2R38 phenotype could provide insight into the inconsistent results obtained from the different studies worldwide. Further study is warranted on the categorization of patients based on their T2R38 phenotype. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Article
The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2
Viruses 2021, 13(3), 425; https://doi.org/10.3390/v13030425 - 06 Mar 2021
Cited by 1 | Viewed by 1302
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to [...] Read more.
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. Recombinant spike and envelope SARS-CoV-2 proteins were disrupted by BromAc. Spike and envelope protein disulfide bonds were reduced by Acetylcysteine. In in vitro whole virus culture of both wild-type and spike mutants, SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Article
Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea
Viruses 2021, 13(2), 329; https://doi.org/10.3390/v13020329 - 20 Feb 2021
Cited by 1 | Viewed by 1290
Abstract
Background: To evaluate the role of hydroxychloroquine (HCQ) as pre-exposure prophylaxis against coronavirus disease 2019 (COVID-19), we investigated the prevalence of positive test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing according to recent HCQ use in patients who had been [...] Read more.
Background: To evaluate the role of hydroxychloroquine (HCQ) as pre-exposure prophylaxis against coronavirus disease 2019 (COVID-19), we investigated the prevalence of positive test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing according to recent HCQ use in patients who had been tested using nationwide health-insurance data of South Korea. Methods: All adults tested for SARS-CoV-2 from 20 January 2020 to 15 May 2020 were identified. HCQ users were defined as patients who had been pretreated with HCQ for at least 30 days until the date of SARS-CoV-2 testing. The prevalence of positive PCR results for SARS-CoV-2 was compared between HCQ users and nonusers. Results: Of a total of 216,686 individuals who had been tested for SARS-CoV-2, 743 (0.3%) were pretreated with HCQ. The prevalence of positive results was not significantly different between HCQ users (2.2%) and nonusers (2.7%; P = 0.35), with an odds ratio of 0.79 (95% confidence interval (CI), 0.48–1.30). Propensity score-matched-cohort analysis showed similar results in terms of the prevalence of positive results (2.2% in HCQ users vs. 3.1% in nonusers; P = 0.18), with an odds ratio of 0.69 (95% CI, 0.40–1.19). The rate of positive PCR was not significantly different in long-term HCQ users (more than 3 or 6 months) compared with nonusers. Conclusions: In this population-based study, recent exposure to HCQ was not significantly associated with a lower risk of SARS-CoV-2 infection. Our data do not support the use of HCQ as pre-exposure prophylaxis against COVID-19. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Article
Structure-Based Identification of Natural Products as SARS-CoV-2 Mpro Antagonist from Echinacea angustifolia Using Computational Approaches
Viruses 2021, 13(2), 305; https://doi.org/10.3390/v13020305 - 15 Feb 2021
Viewed by 1210
Abstract
Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main [...] Read more.
Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (Mpro) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from Echinacea-angustifolia, commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 Mpro. Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>−10 kcal/mol) in the SARS-CoV-2 Mpro catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<−4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 Mpro with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from Echinacea angustifolia for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 Mpro antagonist with higher affinity and drug-likeness. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Review

Jump to: Research, Other

Review
An Appraisal of the Current Scenario in Vaccine Research for COVID-19
Viruses 2021, 13(7), 1397; https://doi.org/10.3390/v13071397 - 18 Jul 2021
Viewed by 645
Abstract
The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still [...] Read more.
The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still remains obscure, ongoing genomic studies have been successful in identifying its genomic sequence and the presenting antigen. These may serve as promising, potential therapeutic targets in the effective management of COVID-19. In an attempt to establish herd immunity, massive efforts have been directed and driven toward developing vaccines against the SARS-CoV-2 pathogen. This review, in this direction, is aimed at providing the current scenario and future perspectives in the development of vaccines against SARS-CoV-2. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Review
Potential Prophylactic Treatments for COVID-19
Viruses 2021, 13(7), 1292; https://doi.org/10.3390/v13071292 - 02 Jul 2021
Viewed by 595
Abstract
The World Health Organization declared the SARS-CoV-2 outbreak a Public Health Emergency of International Concern at the end of January 2020 and a pandemic two months later. The virus primarily spreads between humans via respiratory droplets, and is the causative agent of Coronavirus [...] Read more.
The World Health Organization declared the SARS-CoV-2 outbreak a Public Health Emergency of International Concern at the end of January 2020 and a pandemic two months later. The virus primarily spreads between humans via respiratory droplets, and is the causative agent of Coronavirus Disease 2019 (COVID-19), which can vary in severity, from asymptomatic or mild disease (the vast majority of the cases) to respiratory failure, multi-organ failure, and death. Recently, several vaccines were approved for emergency use against SARS-CoV-2. However, their worldwide availability is acutely limited, and therefore, SARS-CoV-2 is still expected to cause significant morbidity and mortality in the upcoming year. Hence, additional countermeasures are needed, particularly pharmaceutical drugs that are widely accessible, safe, scalable, and affordable. In this comprehensive review, we target the prophylactic arena, focusing on small-molecule candidates. In order to consolidate a potential list of such medications, which were categorized as either antivirals, repurposed drugs, or miscellaneous, a thorough screening for relevant clinical trials was conducted. A brief molecular and/or clinical background is provided for each potential drug, rationalizing its prophylactic use as an antiviral or inflammatory modulator. Drug safety profiles are discussed, and current medical indications and research status regarding their relevance to COVID-19 are shortly reviewed. In the near future, a significant body of information regarding the effectiveness of drugs being clinically studied for COVID-19 is expected to accumulate, in addition to information regarding the efficacy of prophylactic treatments. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Review
Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms
Viruses 2021, 13(4), 700; https://doi.org/10.3390/v13040700 - 18 Apr 2021
Cited by 2 | Viewed by 3081
Abstract
The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such [...] Read more.
The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain–Barré syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Review
Target Product Profile Analysis of COVID-19 Vaccines in Phase III Clinical Trials and Beyond: An Early 2021 Perspective
Viruses 2021, 13(3), 418; https://doi.org/10.3390/v13030418 - 05 Mar 2021
Cited by 5 | Viewed by 4702
Abstract
The coronavirus SARS-CoV-2, which causes Coronavirus disease 2019 (COVID-19), has infected more than 100 million people globally and caused over 2.5 million deaths in just over one year since its discovery in Wuhan, China in December 2019. The pandemic has evoked widespread collateral [...] Read more.
The coronavirus SARS-CoV-2, which causes Coronavirus disease 2019 (COVID-19), has infected more than 100 million people globally and caused over 2.5 million deaths in just over one year since its discovery in Wuhan, China in December 2019. The pandemic has evoked widespread collateral damage to societies and economies, and has destabilized mental health and well-being. Early in 2020, unprecedented efforts went into the development of vaccines that generate effective antibodies to the SARS-CoV-2 virus. Teams developing twelve candidate vaccines, based on four platforms (messenger RNA, non-replicating viral vector, protein/virus-like particle, and inactivated virus) had initiated or announced the Phase III clinical trial stage by early November 2020, with several having received emergency use authorization in less than a year. Vaccine rollout has proceeded around the globe. Previously, we and others had proposed a target product profile (TPP) for ideal/optimal and acceptable/minimal COVID-19 vaccines. How well do these candidate vaccines stack up to a harmonized TPP? Here, we perform a comparative analysis in several categories of these candidate vaccines based on the latest available trial data and highlight the early successes as well as the hurdles and barriers yet to be overcome for ending the global COVID-19 pandemic. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Review
Pharmacogenetics Approach for the Improvement of COVID-19 Treatment
Viruses 2021, 13(3), 413; https://doi.org/10.3390/v13030413 - 05 Mar 2021
Cited by 1 | Viewed by 1335
Abstract
The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. Pharmacogenetics could explain this variation and improve patients’ outcomes with this complex disease; nevertheless, several disease-related [...] Read more.
The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. Pharmacogenetics could explain this variation and improve patients’ outcomes with this complex disease; nevertheless, several disease-related issues must be carefully reviewed in the pharmacogenetic study of COVID-19 treatment. We aimed to describe the pharmacogenetic variants reported for drugs used for COVID-19 treatment (remdesivir, oseltamivir, lopinavir, ritonavir, azithromycin, chloroquine, hydroxychloroquine, ivermectin, and dexamethasone). In addition, other factors relevant to the design of pharmacogenetic studies were mentioned. Variants in CYP3A4, CYP3A5, CYP2C8, CY2D6, ABCB1, ABCC2, and SLCO1B1, among other variants, could be included in pharmacogenetic studies of COVID-19 treatment. Besides, nongenetic factors such as drug–drug interactions and inflammation should be considered in the search for personalized therapy of COVID-19. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Review
Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design
Viruses 2021, 13(1), 109; https://doi.org/10.3390/v13010109 - 14 Jan 2021
Cited by 15 | Viewed by 4121
Abstract
The spike protein in SARS-CoV-2 (SARS-2-S) interacts with the human ACE2 receptor to gain entry into a cell to initiate infection. Both Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 vaccine candidates are based on stabilized mRNA encoding prefusion SARS-2-S that can be produced after the [...] Read more.
The spike protein in SARS-CoV-2 (SARS-2-S) interacts with the human ACE2 receptor to gain entry into a cell to initiate infection. Both Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 vaccine candidates are based on stabilized mRNA encoding prefusion SARS-2-S that can be produced after the mRNA is delivered into the human cell and translated. SARS-2-S is cleaved into S1 and S2 subunits, with S1 serving the function of receptor-binding and S2 serving the function of membrane fusion. Here, I dissect in detail the various domains of SARS-2-S and their functions discovered through a variety of different experimental and theoretical approaches to build a foundation for a comprehensive mechanistic understanding of how SARS-2-S works to achieve its function of mediating cell entry and subsequent cell-to-cell transmission. The integration of structure and function of SARS-2-S in this review should enhance our understanding of the dynamic processes involving receptor binding, multiple cleavage events, membrane fusion, viral entry, as well as the emergence of new viral variants. I highlighted the relevance of structural domains and dynamics to vaccine development, and discussed reasons for the spike protein to be frequently featured in the conspiracy theory claiming that SARS-CoV-2 is artificially created. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Review
Lead SARS-CoV-2 Candidate Vaccines: Expectations from Phase III Trials and Recommendations Post-Vaccine Approval
Viruses 2021, 13(1), 54; https://doi.org/10.3390/v13010054 - 31 Dec 2020
Cited by 17 | Viewed by 4787
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily through respiratory droplets/aerosols and it causes COVID-19. The virus infects epithelial cells by using the spike protein on its surface to bind to angiotensin-converting enzyme 2 receptor on the cells. Thus, candidate vaccines [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily through respiratory droplets/aerosols and it causes COVID-19. The virus infects epithelial cells by using the spike protein on its surface to bind to angiotensin-converting enzyme 2 receptor on the cells. Thus, candidate vaccines targeting the spike protein are currently being developed to prevent against infections. Approximately 44 SARS-CoV-2 candidate vaccines are in clinical trials (phase I–III) and an additional 164 candidates are in preclinical stages. The efficacy data from phase I/II trials of lead candidate vaccines look very promising with virus-neutralizing geometric mean antibody titers in the range of 16.6–3906. Most recently, two SARS-CoV-2 candidate vaccines, BNT162b2 and mRNA-1273, have been granted the first emergency use authorization (EUA) in the U.S.; BNT162b2 has also been granted an EUA in the United Kingdom, Canada, and in the European Union. This review assesses whether SARS-CoV-2 candidate vaccines (with approved EUA or in phase III trials) meet the criteria for an ideal SARS-CoV-2 vaccine. The review concludes with expectations from phase III trials and recommendations for phase IV studies (post-vaccine approval). Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Other

Jump to: Research, Review

Brief Report
Effect of Aprotinin and Avifavir® Combination Therapy for Moderate COVID-19 Patients
Viruses 2021, 13(7), 1253; https://doi.org/10.3390/v13071253 - 27 Jun 2021
Viewed by 741
Abstract
COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir® or Hydroxychloroquine (HCQ) drugs, which are recommended by the Russian Ministry [...] Read more.
COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir® or Hydroxychloroquine (HCQ) drugs, which are recommended by the Russian Ministry of Health for the treatment therapy of moderate COVID-19 patients. This prospective single-center study included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2, and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU four times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). In cohorts 1–3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of the combination therapy in cohort 3 was the most prominent, and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0–4.0), normalization of the CRP concentration was 3.5 days (IQR 3–5), of the D-dimer concentration was 5 days (IQR 4 to 5); body temperature was 1 day (IQR 1–3), improvement in clinical status or discharge from the hospital was 5 days (IQR 5–5), and improvement in lung lesions of patients on 14 day was 100%. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Brief Report
Amantadine Inhibits SARS-CoV-2 In Vitro
Viruses 2021, 13(4), 539; https://doi.org/10.3390/v13040539 - 24 Mar 2021
Cited by 1 | Viewed by 5361
Abstract
Since the SARS-CoV-2 pandemic started in late 2019, the search for protective vaccines and for drug treatments has become mandatory to fight the global health emergency. Travel restrictions, social distancing, and face masks are suitable counter measures, but may not bring the pandemic [...] Read more.
Since the SARS-CoV-2 pandemic started in late 2019, the search for protective vaccines and for drug treatments has become mandatory to fight the global health emergency. Travel restrictions, social distancing, and face masks are suitable counter measures, but may not bring the pandemic under control because people will inadvertently or at a certain degree of restriction severity or duration become incompliant with the regulations. Even if vaccines are approved, the need for antiviral agents against SARS-CoV-2 will persist. However, unequivocal evidence for efficacy against SARS-CoV-2 has not been demonstrated for any of the repurposed antiviral drugs so far. Amantadine was approved as an antiviral drug against influenza A, and antiviral activity against SARS-CoV-2 has been reasoned by analogy but without data. We tested the efficacy of amantadine in vitro in Vero E6 cells infected with SARS-CoV-2. Indeed, amantadine inhibited SARS-CoV-2 replication in two separate experiments with IC50 concentrations between 83 and 119 µM. Although these IC50 concentrations are above therapeutic amantadine levels after systemic administration, topical administration by inhalation or intranasal instillation may result in sufficient amantadine concentration in the airway epithelium without high systemic exposure. However, further studies in other models are needed to prove this hypothesis. Full article
(This article belongs to the Special Issue Vaccines and Therapeutics against Coronaviruses)
Show Figures

Figure 1

Back to TopTop