A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2

Kim, Kwang Su; Ejima, Keisuke; Iwanami, Shoya; Fujita, Yasuhisa; Ohashi, Hirofumi; Koizumi, Yoshiki; Asai, Yusuke; Nakaoka, Shinji; Watashi, Koichi; Aihara, Kazuyuki; Thompson, Robin N.; Ke, Ruian; Perelson, Alan S.; Iwami, Shingo

doi:10.1371/journal.pbio.3001128

A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2

Journal Article · Mon Mar 22 00:00:00 EDT 2021 · PLoS Biology (Online)

DOI:https://doi.org/10.1371/journal.pbio.3001128· OSTI ID:1815799

^[1]; ^[2]; ^[3]; ^[3]; Ohashi, Hirofumi ^[4]; Koizumi, Yoshiki ^[5]; Asai, Yusuke ^[5]; Nakaoka, Shinji ^[6]; Watashi, Koichi ^[7]; Aihara, Kazuyuki ^[8]; ^[9]; ^[10]; ^[10]; ^[11]

Kyushu Univ., Fukuoka (Japan). Faculty of Sciences. Dept. of Biology; OSTI
Indiana Univ., Bloomington, IN (United States). School of Public Health. Dept. of Epidemiology and Biostatistics
Kyushu Univ., Fukuoka (Japan). Faculty of Sciences. Dept. of Biology
National Inst. of Infectious Diseases, Tokyo (Japan). Dept. of Virology II
National Center for Global Health and Medicine, Tokyo (Japan)
Hokkaido Univ., Sapporo (Japan). Faculty of Advanced Life Science
National Inst. of Infectious Diseases, Tokyo (Japan). Dept. of Virology II; Tokyo Univ. of Science, Chiba (Japan). Dept. of Applied Biological Science; Kyoto Univ. (Japan). Inst. for Frontier Life and Medical Sciences; Japan Science and Technology Agency, Saitama (Japan). JST--Mirai
Univ. of Tokyo (Japan). Univ.y of Tokyo Insts. for Advanced Study. International Research Center for Neurointelligence
Univ. of Warwick, Coventry (United Kingdom). Mathematics Inst.; Univ. of Warwick, Coventry (United Kingdom). Zeeman Inst. for Systems Biology and Infectious Disease Epidemiology Research
New Mexico Consortium, Los Alamos, NM (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics Group
Kyushu Univ., Fukuoka (Japan). Faculty of Sciences. Dept. of Biology; Japan Science and Technology Agency, Saitama (Japan). JST--Mirai; Kyoto Univ. (Japan). Inst. for the Advanced Study of Human Biology; Japanese Foundation for Cancer Research, Tokyo (Japan). NEXT--Ganken Program; Science Groove, Fukuoka (Japan)

The scientific community is focused on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease 2019 (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data, we compare within-host viral dynamics of SARS-CoV-2 with analogous dynamics of MERS-CoV and SARS-CoV. Our quantitative analyses using a mathematical model revealed that the within-host reproduction number at symptom onset of SARS-CoV-2 was statistically significantly larger than that of MERS-CoV and similar to that of SARS-CoV. In addition, the time from symptom onset to the viral load peak for SARS-CoV-2 infection was shorter than those of MERS-CoV and SARS-CoV. These findings suggest the difficulty of controlling SARS-CoV-2 infection by antivirals. We further used the viral dynamics model to predict the efficacy of potential antiviral drugs that have different modes of action. The efficacy was measured by the reduction in the viral load area under the curve (AUC). Our results indicate that therapies that block de novo infection or virus production are likely to be effective if and only if initiated before the viral load peak (which appears 2–3 days after symptom onset), but therapies that promote cytotoxicity of infected cells are likely to have effects with less sensitivity to the timing of treatment initiation. Furthermore, combining a therapy that promotes cytotoxicity and one that blocks de novo infection or virus production synergistically reduces the AUC with early treatment. Our unique modeling approach provides insights into the pathogenesis of SARS-CoV-2 and may be useful for development of antiviral therapies.

View Accepted Manuscript (DOE)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Research Foundation of Korea; JSPS Scientific Research (KAKENHI); Moonshot R&D; National Science Foundation (NSF)

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1815799

Journal Information:: PLoS Biology (Online), Journal Name: PLoS Biology (Online) Journal Issue: 3 Vol. 19; ISSN 1545-7885

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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