High-Throughput Computational Discovery of Anti-Coronavirus Agents in the COVID-19 Era: Crucial Insights for Combating Emerging Biogenic Threats

Dmitry S. Druzhilovskiy; Dmitry A. Filimonov; Pavel V. Pogodin; Anastasia V. Rudik; Leonid A. Stolbov; Olga A. Tarasova; Alexander V. Veselovsky; Vladimir V. Poroikov

doi:10.14529/jsfi260107

Authors

Dmitry S. Druzhilovskiy Institute of Biomedical Chemistry (IBMC), Moscow, Russian Federation https://orcid.org/0000-0001-9024-1331
Dmitry A. Filimonov Institute of Biomedical Chemistry (IBMC), Moscow, Russian Federation https://orcid.org/0000-0002-0339-8478
Pavel V. Pogodin Institute of Biomedical Chemistry (IBMC), Moscow, Russian Federation https://orcid.org/0000-0003-1843-7668
Anastasia V. Rudik Institute of Biomedical Chemistry (IBMC), Moscow, Russian Federation https://orcid.org/0000-0002-8916-9675
Leonid A. Stolbov Institute of Biomedical Chemistry (IBMC), Moscow, Russian Federation https://orcid.org/0000-0002-3258-8350
Olga A. Tarasova Institute of Biomedical Chemistry (IBMC), Moscow, Russian Federation https://orcid.org/0000-0002-3723-7832
Alexander V. Veselovsky Institute of Biomedical Chemistry (IBMC), Moscow, Russian Federation https://orcid.org/0000-0001-6362-7757
Vladimir V. Poroikov Institute of Biomedical Chemistry (IBMC), Moscow, Russian Federation https://orcid.org/0000-0001-7937-2621

DOI:

https://doi.org/10.14529/jsfi260107

Keywords:

COVID-19, JEDI COVID-19 challenge, anti-coronavirus agents, in silico screening, future biogenic threats, effective response

Abstract

In May 2020, the Joint European Disruptive Initiative (JEDI) launched the “Billion Molecules against COVID 19” challenge – an extensive open science effort aimed at identifying small molecule inhibitors of SARS-CoV-2 and related human receptors. Our research group joined this initiative among 130 international teams, focusing on the in silico screening for potential anti coronavirus agents that target three viral proteins and one human receptor. The screening campaign covered more than one billion synthetically accessible structures, including approved pharmaceuticals. By July 17, 2020, our team submitted a subset of 10000 prioritized compounds to the organizers for expert evaluation. The results from our selection, together with those from 19 other participating teams, contributed to a pool of approximately 1000 molecules selected for chemical synthesis and bioactivity testing. In total, 878 compounds were successfully synthesized and evaluated for inhibitory activity against various SARS-CoV-2 targets as well as the human serine protease TMPRSS2. Ultimately, 27 compounds – including one proposed by our group – demonstrated measurable anti coronavirus activity. The collective outcomes of these collaborative efforts were reported in the “Molecular Informatics” journal in 2024. In the present study, we summarize our participation in the JEDI challenge and discuss broader methodological and organizational considerations critical for improving the efficiency of rapid scientific responses to future emerging biological threats.

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