Quantifying the effect of trypsin and elastase on in vitro SARS-CoV infections

• Published in: Virus research 2021-07, Vol.299, p.198423-198423, Article 198423
• Main Authors: Rodriguez, Thalia, Dobrovolny, Hana M.
• Format: Article
• Language: English
• Subjects: Animals; Chlorocebus aethiops; Coronavirus; COVID-19 - virology; In vitro infections; Mathematical model; Models, Theoretical; Pancreatic Elastase - pharmacology; Parameter estimation; Protease; SARS-CoV-2 - drug effects; SARS-CoV-2 - physiology; Trypsin - pharmacology; Vero Cells; Viral Load; Virus Internalization - drug effects; Virus Replication - drug effects
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2021.198423

•The paper presents an analysis of the effect of proteases on in vitro SARS-CoV infections using mathematical modeling.•We find that the addition of trypsin alters viral kinetics at all points of the viral replication cycle.•The effect of elastase is more limited and does not appear to significantly alter viral production or infecting time.•Our results indicate that the addition of proteases alters more than just viral entry during SARS-CoV infections. The SARS coronavirus (SARS-CoV) has the potential to cause serious disease that can spread rapidly around the world. Much of our understanding of SARS-CoV pathogenesis comes from in vitro experiments. Unfortunately, in vitro experiments cannot replicate all the complexity of the in vivo infection. For example, proteases in the respiratory tract cleave the SARS-CoV surface protein to facilitate viral entry, but these proteases are not present in vitro. Unfortunately, proteases might also have an effect on other parts of the replication cycle. Here, we use mathematical modeling to estimate parameters characterizing viral replication for SARS-CoV in the presence of trypsin or elastase, and in the absence of either. In addition to increasing the infection rate, the addition of trypsin and elastase causes lengthening of the eclipse phase duration and the infectious cell lifespan.