Safety and immunogenicity of the ChAdOx1, MVA-MERS-S, and GLS-5300 DNA MERS-CoV vaccines.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a pathogen associated with an acute respiratory infection that has a high mortality rate in humans. It was first identified in June of 2012 in the Arabian Peninsula. The success of the COVID-19 vaccines has shown that it is possible to take advantage of medical and scientific advances to produce safe and effective vaccines for coronaviruses. This study aimed to examine the safety and immunogenicity of MERS-CoV vaccines. METHODS: The research method Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used as the guideline for this study. RevMan 5.4 software was used to perform a meta-analysis of the included studies. The safety was assessed by recording adverse events following vaccination, and the immunogenicity was assessed by using seroconversion. RESULTS: The study included five randomized controlled trials that met the inclusion criteria after screening. The studies had 173 participants and were performed in four countries. The vaccines examined were the ChAdOx1 MERS vaccine, MVA-MERS-S vaccine, and GLS-5300 DNA MERS-CoV vaccine. The meta-analysis showed no significant differences in local adverse effects (all local adverse effects and pain) or systemic adverse effects (all systemic adverse effects, fatigue, and headache) among participants in groups receiving a high-dose vaccine or a low-dose vaccine. There were, however, higher levels of seroconversion in high-dose groups than in low-dose groups (OR 0.16 [CI 0.06, 0.42, p = 0.0002]). CONCLUSION: The findings showed that high doses of current MERS-CoV vaccine candidates conferred better immunogenicity than low doses and that there were no differences in the safety of the vaccines.

The Safety and Efficacy of the Protease Inhibitors Lopinavir/Ritonavir as Monotherapy or Combined with Interferon in COVID-19 Patients

Enzyme inhibitors are frequently used to treat viral illnesses. Protease inhibitors are a promising class for combating novel and life-threatening viral infections. This research aimed to evaluate the efficacy and safety of lopinavir/ritonavir monotherapy or lopinavir/ritonavir plus interferon for the treatment of COVID-19. The PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for English articles with full texts available online. ReviewManager software was used to conduct a meta-analysis, subgroup analysis, and sensitivity analysis. Following the creation of the protocol, the collected sources were sorted into categories and evaluated for quality. Risk and hazard ratios and the random effects model were implemented, with statistical heterogeneity assigned using the Higgins I2 statistic. Lopinavir/ritonavir, with or without interferon, was associated with a nonsignificant higher mortality rate (odds ratio [OR] 1.29;95% confidence interval [CI] 0.95 to 1.761;p = 0.1), as was clinical improvement (OR 1.2;95% CI 0.8 to 1.84;p = 0.36). The difference in the length of hospital stay was in favor of the control group but statistically insignificant (standardized mean difference [SMD] 0.07;95% CI -0.44 to 0.57;p = 0.79). The pooled data showed that lopinavir/ritonavir, with or without interferon, was associated with a significantly higher number of adverse events than placebo (OR 1.2;95% CI 1.09 to 2.34;p = 0.02). Serious adverse events were insignificantly increased in the treated group over the control group (OR 1.2;95% CI 0.96 to 2.12;p = 0.08). In the subgroup analysis, it was found that interferon used with lopinavir/ritonavir did not have a statistically significant effect on mortality rates (OR 1.75;95% CI 0.87 to 3.55;p = 0.37), adverse effects (OR 1.20;95% CI 0.75 to 1.91;p = 0.27), or serious adverse effects (OR 1.86;95% CI 1.17 to 2.96;p = 0.33). Treatment with lopinavir/ritonavir alone or in combination with interferon for COVID-19 did not significantly outperform placebo in this study. Large randomized clinical trials are required to evaluate lopinavir/ritonavir in conjunction with interferon for the treatment of COVID-19. Such studies would benefit greatly from being conducted in a double-blind fashion at multiple locations.

SARS CoV-2 Organotropism Associated Pathogenic Relationship of Gut-Brain Axis and Illness.

COVID-19 has resulted in a pandemic after its first appearance in a pneumonia patient in China in early December 2019. As per WHO, this global outbreak of novel COVID-19 has resulted in 28,329,790 laboratory-confirmed cases and 911,877 deaths which have been reported from 210 countries as on 12th Sep 2020. The major symptoms at the beginning of COVID-19 are fever (98%), tussis (76%), sore throat (17%), rhinorrhea (2%), chest pain (2%), and myalgia or fatigue (44%). Furthermore, acute respiratory distress syndrome (61.1%), cardiac dysrhythmia (44.4%), shock (30.6%), hemoptysis (5%), stroke (5%), acute cardiac injury (12%), acute kidney injury (36.6%), dermatological symptoms with maculopapular exanthema (36.1%), and death can occur in severe cases. Even though human coronavirus (CoV) is mainly responsible for the infections of the respiratory tract, some studies have shown CoV (in case of Severe Acute Respiratory Syndrome, SARS and Middle East Respiratory Syndrome, MERS) to possess potential to spread to extra-pulmonary organs including the nervous system as well as gastrointestinal tract (GIT). Patients infected with COVID-19 have also shown symptoms associated with neurological and enteric infection like disorders related to smell/taste, loss of appetite, nausea, emesis, diarrhea, and pain in the abdomen. In the present review, we attempt to evaluate the understanding of basic mechanisms involved in clinical manifestations of COVID-19, mainly focusing on interaction of COVID-19 with gut-brain axis. This review combines both biological characteristics of the virus and its clinical manifestations in order to comprehend an insight into the fundamental potential mechanisms of COVID-19 virus infection, and thus endorse in the advancement of prophylactic and treatment strategies.

Repurposing of FDA-approved antivirals, antibiotics, anthelmintics, antioxidants, and cell protectives against SARS-CoV-2 papain-like protease.

SARS-CoV-2 or Coronavirus disease 19 (COVID-19) is a rapidly spreading, highly contagious, and sometimes fatal disease for which drug discovery and vaccine development are critical. SARS-CoV-2 papain-like protease (PLpro) was used to virtually screen 1697 clinical FDA-approved drugs. Among the top results expected to bind with SARS-CoV-2 PLpro strongly were three cell protectives and antioxidants (NAD+, quercitrin, and oxiglutatione), three antivirals (ritonavir, moroxydine, and zanamivir), two antimicrobials (doripenem and sulfaguanidine), two anticancer drugs, three benzimidazole anthelmintics, one antacid (famotidine), three anti-hypertensive ACE receptor blockers (candesartan, losartan, and valsartan) and other miscellaneous systemically or topically acting drugs. The binding patterns of these drugs were superior to the previously identified SARS CoV PLpro inhibitor, 6-mercaptopurine (6-MP), suggesting a potential for repurposing these drugs to treat COVID-19. The objective of drug repurposing is the rapid relocation of safe and approved drugs by bypassing the lengthy pharmacokinetic, toxicity, and preclinical phases. The ten drugs with the highest estimated docking scores with favorable pharmacokinetics were subjected to molecular dynamics (MD) simulations followed by molecular mechanics/generalized Born surface area (MM/GBSA) binding energy calculations. Phenformin, quercetin, and ritonavir all demonstrated prospective binding affinities for COVID-19 PLpro over 50 ns MD simulations, with binding energy values of -56.6, -40.9, and -37.6 kcal/mol, respectively. Energetic and structural analyses showed phenformin was more stable than quercetin and ritonavir. The list of the drugs provided herein constitutes a primer for clinical application in COVID-19 patients and guidance for further antiviral studies.Communicated by Ramaswamy H. Sarma.