key: cord-0874030-f8vho1un
authors: Kudryashova, Elena; Zani, Ashley; Vilmen, Geraldine; Sharma, Amit; Lu, Wuyuan; Yount, Jacob S.; Kudryashov, Dmitri S.
title: SARS-CoV-2 inactivation by human defensin HNP1 and retrocyclin RC-101
date: 2021-05-27
journal: bioRxiv
DOI: 10.1101/2021.05.27.445985
sha: d99e8477c4a19a6dde7605227b7e4cdc90c45f7b
doc_id: 874030
cord_uid: f8vho1un

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is an enveloped virus responsible for the COVID-19 respiratory disease pandemic. While induction of adaptive antiviral immunity via vaccination holds promise for combatting the pandemic, the emergence of new potentially more transmissible and vaccine-resistant variants of SARS-CoV-2 is an ever-present threat. Thus, it remains essential to better understand innate immune mechanisms that are active against the virus. One component of the innate immune system with broad anti-pathogen, including antiviral, activity is a group of cationic immune peptides termed defensins. The defensins’ ability to neutralize enveloped and non-enveloped viruses and to inactivate numerous bacterial toxins correlate with their ability to promote the unfolding of thermodynamically pliable proteins. Accordingly, we found that human neutrophil a-defensin HNP1 and retrocyclin RC-101 destabilize SARS-CoV-2 Spike protein and interfere with Spike-mediated membrane fusion and SARS-CoV-2 infection in cell culture. We show that HNP1 binds to Spike with submicromolar affinity. Although binding of HNP1 to serum albumin is more than 20-fold weaker, serum reduces the anti-SARS-CoV-2 activity of HNP1. At high concentrations of HNP1, its ability to inactivate the virus was preserved even in the presence of serum. These results suggest that specific a- and 8-defensins may be valuable tools in developing SARS-CoV-2 infection prevention strategies.

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