The cleavage potential of cross-species TMPRSS2 variants toward SARS-CoV-2

Tyshawn Ferrell 1,2, Kelly Pierce 1, Johnny Aldan1,3, Ethan Ho 1, Dairian Balai 1,3 1Texas Advanced Computing Center, University of Texas at Austin, 10100 Burnet Rd (R8700), Austin, TX 78758 2Department of Biology, Albany State University, 504 College Drive, Albany, GA 31705 3 Department of Natural Sciences and Mathematics, Chaminade University of Honolulu, 3140 Waialae Avenue, Honolulu, HI 96816

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-stranded RNA virus, has caused >1,000,000 infections and >100,000 deaths during the 2020 pandemic. Its successful infectivity is in part due to structural motifs and specific cell receptor targeting. The SARS-CoV-2 spike (S) glycoprotein mediates cell attachment by recognizing the angiotensin converting enzyme II (ACE2) receptor, which initializes cleavage by host cell proteases to induce cell membrane fusion. Previous studies have shown that transmembrane protease/serine subfamily member 2 (TMPRSS2) increases cleavage efficiency towards the S protein subunits. This study aims to characterize cross-species variants of TMPRSS2 at specific positions responsible for this catalytic processing. We hypothesize that TMPRSS2 aids in the spillover of SARS-CoV-2 to alternate hosts by having a conserved binding region. We investigated the conservation of TMPRSS2 sequences amongst several species in silica. We utilized protein databanks to form concise TMPRSS2 amino acid sequence alignments of six domestic mammals for comparisons with the human variant. We characterized differences in catalytically important residues based off the position specific frequency and changes in amino acid properties. We found that important residues within TMPRSS2 are highly conserved, but there is slight variation in certain domains. This study provides insight on possible spillover into alternate host with structurally similar TMPRSS2 variants compared to human homologs, which could facilitate epidemics in domesticated animal populations.

Additional Abstract Information

Presenter: Tyshawn Ferrell

Institution: Albany State University

Type: Poster

Subject: Biochemistry

Status: Approved

Time and Location

Session: Poster 1
Date/Time: Mon 1:30pm-2:30pm
Session Number: 2136