Hidden in Plain Sight: Natural Products of Commensal Microbiota as an Environmental Selection Pressure for the Rise of New Variants of SARS‐CoV‐2

TY - JOUR

T1 - Hidden in Plain Sight: Natural Products of Commensal Microbiota as an Environmental Selection Pressure for the Rise of New Variants of SARS‐CoV‐2

AU - Dragelj, Jovan

AU - Mroginski, Maria Andrea

AU - H. Ebrahimi, Kourosh

N1 - Funding Information: K.H.E. thanks Professor Fraser A. Armstrong (University of Oxford) and Professor Wilfred R. Hagen (TU Delft), Professor William James (University of Oxford) and Professor James McCullagh (University of Oxford) for their generous support. K.H.E. is grateful to the European Molecular Biology Organization (EMBO) (EMBO ALTF 157-2015), COST (European Cooperation in Science and Technology) Action CA15133 (ECOST-STSM-Request-CA15133-44200), and CRUK Oxford Developmental Fund (CRUKDF-0221-KHE) for generous financial support of his research. M.A.M. and J.D. acknowledge funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy ? EXC 2008-390540038-UniSysCat. Funding Information: K.H.E. thanks Professor Fraser A. Armstrong (University of Oxford) and Professor Wilfred R. Hagen (TU Delft), Professor William James (University of Oxford) and Professor James McCullagh (University of Oxford) for their generous support. K.H.E. is grateful to the European Molecular Biology Organization (EMBO) (EMBO ALTF 157‐2015), COST (European Cooperation in Science and Technology) Action CA15133 (ECOST‐STSM‐Request‐CA15133‐44200), and CRUK Oxford Developmental Fund (CRUKDF – 0221 – KHE) for generous financial support of his research. M.A.M. and J.D. acknowledge funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy ‐ EXC 2008 – 390540038 – UniSysCat. Publisher Copyright: © 2021 Wiley-VCH GmbH

PY - 2021/10/13

Y1 - 2021/10/13

N2 - Since the emergence of SARS‐CoV‐2, little attention has been paid to the interplay between the interaction of virus and commensal microbiota. Here, we used molecular docking and dynamics simulations to study the interaction of some of the known metabolites and natural products (NPs) produced by commensal microbiota with the receptor binding domain (RBD) of the spike glycoprotein of SARS‐CoV‐2. The results predict that NPs of commensal microbiota such as bile acids and non‐ribosomal peptides (NRPs), of which some are siderophores, bind to the wild‐type RBD and interfere with its binding to the ACE2 receptor. N501Y mutation, which is present in many of the emerging variants of the virus, abolishes the predicted binding pocket of bile acids and NRPs. Based on these findings, available experimental data showing that bile acids reduce the binding affinity of wild‐type RBD to the ACE2 receptor, and the data suggesting that the respiratory tract microbiota affect viral infection we put forward the following proposal: mutations such as N501Y enable the RBD to bind to the ACE2 receptor more effectively in the presence of NPs produced by the respiratory tract bacteria thereby, increasing the infectivity rate of the virus. We hope our data stimulate future works to better understand the interactions of NPs produced by commensal microbiota with respiratory viruses like SARS‐CoV‐2.

AB - Since the emergence of SARS‐CoV‐2, little attention has been paid to the interplay between the interaction of virus and commensal microbiota. Here, we used molecular docking and dynamics simulations to study the interaction of some of the known metabolites and natural products (NPs) produced by commensal microbiota with the receptor binding domain (RBD) of the spike glycoprotein of SARS‐CoV‐2. The results predict that NPs of commensal microbiota such as bile acids and non‐ribosomal peptides (NRPs), of which some are siderophores, bind to the wild‐type RBD and interfere with its binding to the ACE2 receptor. N501Y mutation, which is present in many of the emerging variants of the virus, abolishes the predicted binding pocket of bile acids and NRPs. Based on these findings, available experimental data showing that bile acids reduce the binding affinity of wild‐type RBD to the ACE2 receptor, and the data suggesting that the respiratory tract microbiota affect viral infection we put forward the following proposal: mutations such as N501Y enable the RBD to bind to the ACE2 receptor more effectively in the presence of NPs produced by the respiratory tract bacteria thereby, increasing the infectivity rate of the virus. We hope our data stimulate future works to better understand the interactions of NPs produced by commensal microbiota with respiratory viruses like SARS‐CoV‐2.

UR - http://www.scopus.com/inward/record.url?scp=85111409411&partnerID=8YFLogxK

U2 - 10.1002/cbic.202100346

DO - 10.1002/cbic.202100346

M3 - Article

SN - 1439-4227

VL - 22

SP - 2946

EP - 2950

JO - Chembiochem : a European journal of chemical biology

JF - Chembiochem : a European journal of chemical biology

IS - 20

ER -