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

Abstract

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.

Host Cell Proteases Involved in Human Respiratory Viral Infections and Their Inhibitors: A Review

“…Influenza virus [33] KLK5 X(aliphatic/aromatic)-R/K -X(polar/aliphatic)-R↓ [30] Influenza virus [33] Neutrophil elastase A/V/I/T↓ [34] Mammalian Orthoreovirus [35], SARS-CoV-1 [36,37] PC5/6 R-X-R/K-R↓ [38] Influenza virus [39], RSV [39] Plasmin R/L↓ [40], preference for aromatic hydrophobic residue at P2 [41] Influenza virus [42], RSV [43], SARS-CoV-1 [44], SARS-CoV-2 [45] Thrombin L-X-P-R↓S/A/G/T-X(aromatic)-R [46] RSV [43], SARS-CoV-2 [21] Trypsin K/R↓ [34] SARS-CoV-1 [47,48], HMPV [49], RSV [43], HPIV [50] Cathepsin G Preference for F, Y, W, or L at P1 [51], S at P6, negatively charged amino acid in P2 position Mammalian Orthoreovirus [18], RSV [52] 3.1. Furin…”