The pandemic caused by the novel betacoronavirus SARS-CoV-2 has already claimed more than 3.5 million lives. Despite the development and use of anti-COVID-19 vaccines, the disease remains a major public health challenge throughout the world. Large-scale screening of the drugs already approved for the treatment of other viral, bacterial, and parasitic infections, as well as autoimmune, oncological, and other diseases is currently underway as part of their repurposing for development of effective therapeutic agents against SARS-CoV-2. In this work, we present the results of a phenotypic screening of libraries of modified heterocyclic bases and 5-norcarbocyclic nucleoside analogs previously synthesized by us. We identified two leading compounds with apparent potential to inhibit SARS-CoV-2 replication and EC50 values in a range of 2070 M. The structures of these compounds can be further optimized to develop an antiviral drug.

BackgroundEffective response to emerging pandemic threats is complicated by the need to develop specific vaccines and other medical products. The availability of broadly specific countermeasures that could be deployed early in the pandemic could significantly alter its course and save countless lives. Live attenuated vaccines (LAVs) were shown to induce non-specific protection against a broad spectrum of off-target pathogens by stimulating innate immune responses. The purpose of this study was to evaluate the effect of immunization with bivalent Oral Poliovirus Vaccine (bOPV) on the incidence of COVID-19 and other acute respiratory infections (ARIs).Methods and FindingsA randomized parallel-group comparative study was conducted in Kirov Medical University. 1115 healthy volunteers aged 18 to 65 were randomized into two equal groups, one of which was immunized orally with a single dose of bOPV “BiVac Polio” and another with placebo. The study participants were monitored for three months for respiratory illnesses including COVID-19. The endpoint was the incidence of acute respiratory infections and laboratory confirmed COVID-19 in both groups during 3 months after immunization. The number of laboratory-confirmed cases of COVID-19 was significantly lower in the vaccinated group than in placebo (25 cases vs. 44, p=0.036). The difference between the overall number of clinically diagnosed respiratory illnesses in the two groups was not statistically significant.ConclusionsImmunization with bOPV reduced the number of laboratory-confirmed COVID-19 cases, consistent with the original hypothesis that LAVs induce non-specific protection against off-target infections. The findings are in line with previous observations of the protective effects of OPV against seasonal influenza and other viral and bacterial pathogens. The absence of a statistically significant effect on the total number of ARIs may be due to the insufficient number of participants and heterogeneous etiology of ARIs. OPV could be used to complement specific coronavirus vaccines, especially in regions of the world where the vaccines are unavailable, and as a stopgap measure for urgent response to future emerging infections. Clinical trial registration number NCT05083039 at clinicaltrals.gov https://clinicaltrials.gov/ct2/show/NCT05083039?term=NCT05083039&draw=2&rank=1

In the search for anti-SARS-CoV-2 drugs, much attention is given to safe and widely available native compounds. The green tea component epigallocatechin 3 gallate (EGCG) is particularly promising because it reportedly inhibits viral replication and viral entry in vitro . However, conclusive evidence for its predominant activity is needed. We tested EGCG effects on the native virus isolated from COVID-19 patients in two independent series of experiments using VERO cells and two different treatment schemes in each series. The results confirmed modest cytotoxicity of EGCG and its substantial antiviral activity. The preincubation scheme aimed at infection prevention has proven particularly beneficial. We complemented that finding with a detailed investigation of EGCG interactions with viral S-protein subunits, including S2, RBD, and the RBD mutant harboring the N501Y mutation. Molecular modeling experiments revealed N501Y-specific stacking interactions in the RBD-ACE2 complex and provided insight into EGCG interference with the complex formation. Together, these findings provide a molecular basis for the observed EGCG effects and reinforce its prospects in COVID-19 prevention therapy.