Detailed Molecular Interactions of Favipiravir with SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza Virus Polymerases In Silico

Microorganisms - Tập 8 Số 10 - Trang 1610
Mitsuru Sada1,2, Takeshi Saraya2, Haruyuki Ishii2, Kaori Okayama3, Yuriko Hayashi3, Takeshi Tsugawa4, Atsuyoshi Nishina5, Koichi Murakami6, Makoto Kuroda7, Akihide Ryo8, Hirokazu Kimura9,8
1Advanced Medical Science Research Center, Gunma Paz University, Shibukawa, Gunma 377-0008, Japan
2Department of Respiratory medicine, Kyorin University Hospital of medicine, Mitaka, Tokyo 181-8611, Japan
3School of Medical Technology, Faculty of Health Science, Gumma Paz University, Takasaki, Gunma 370-0006, Japan
4Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8543, Japan
5College of Science and Technology, Nihon University, Tokyo 101-0062, Japan
6Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
7Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
8Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Kanagawa 236-0004, Japan
9Department of Health Science, Gunma Paz University Graduate School of Health Sciences, Takasaki, Gunma 370-0006, Japan

Tóm tắt

Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5′-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses.

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Microorganisms

Tập 8 Số 10

1610

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