Antiviral Activity of 5-chloropyridin-3-yl-1h-indole-4-carboxylate (AMND) Against COVID-19

Introduction. The viral disease COVID-19 has caused a global emergency. The rapid and widespread spread of COVID-19 and the urgent need for etiotropic drugs have sparked interest in repositioning existing drugs. SARS-CoV proteases (Mpro) and papain protease (PLpro) have been identified as attractive targets for the development of antiviral agents. The aim of this work was to evaluate the antiviral efficacy of indole chloropyridinyl ethers against the SARS-CoV-2 virus in vitro, as well as against the experimental form of COVID-19 in Syrian golden hamsters. Material and methods . The experiments were carried out on a permanent culture of African green monkey kidney cells — Vero Cl008. The effectiveness of the drugs was assessed by suppressing the reproduction of the virus in vitro. Biological activity was assessed by titration of the viruscontaining suspension in Vero Cl008 cell culture by the formation of negative colonies. Syrian golden hamsters orally infected with the SARS-CoV-2 virus, variant B, were used. The effectiveness of the drug was assessed by the coefficient of therapeutic action. Results. The antiviral efficacy of indole chloropyridinyl ethers against the new pandemic virus SARSCoV-2 was studied in vitro during experiments in Vero C1008 cell culture. The results of the study revealed that the drugs effectively suppress the reproduction of the virus when applied after infection. In the concentration range of 12.5–50.0 µg/ml, the drugs almost completely suppress the reproduction of the SARS-CoV-2 virus. According to the complex of clinical, virological, biochemical, and hematological indicators, the disease severity indех (DSI) and the therapeutic action coefficient (TAC) were calculated. For AMND-1X — the DSI was 0.635; the TAC was 36.5%; for AMND-1OL-3 — the DSI was 0.115; the TAC was 88.5%. Conclusion. Of the studied compounds, the drug AMND-1OL-3 showed the highest antiviral activity.