Identification of the peptide derived from S1 domain that inhibits type I and type II feline infectious peritonitis virus infection

Abstract

Feline infectious peritonitis virus (FIPV) can cause a lethal disease in cats, feline infectious peritonitis (FIP). A therapeutic drug that is effective against FIP has not yet been developed. Peptides based on viral protein amino acid sequences have recently been attracting attention as new antiviral drugs. In the present study, we synthesized 30 overlapping peptides based on the amino acid sequence of the S1 domain of the type I FIPV strain KU-2 S protein, and investigated their inhibitory effects on FIPV infection. To evaluate the inhibitory effects on type I FIPV infection of these peptides, we investigated a method to increase the infection efficiency of poorly replicative type I FIPV. The efficiency of type I FIPV infection was increased by diluting the virus with medium containing a polycation. Of the 30 peptides, I-S1-8 (S461-S480), I-S1-9 (S471-S490), I-S1-10 (S481-S500), I-S1-16 (S541-S560), and I-S1-22 (S601-S620) significantly decreased the infectivity of FIPV strain KU-2 while I-S1-9 and I-S1-16 exhibited marked inhibitory effects on FIPV infection. The inhibitory effects on FIPV infection of these 2 peptides on other type I and type II FIPV strains, feline herpesvirus (FHV), and feline calicivirus (FCV) were also examined. These 2 peptides specifically inhibited type I and type II FIPV, but did FHV or FCV infection. In conclusion, the possibility of peptides derived from the S protein of type I FIPV strain KU-2 as anti-FIPV agents effective not only for type I, but also type II FIPV was demonstrated in vitro.

Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus

“…Previously, a coronaviral protease inhibitor GC376 demonstrated a promising advance in direct inhibition of virus replication in a clinical trial 19 . Other pathogen-targeted antiviral approaches have been tested in vitro , awaiting further efficacy validation in vivo 20 – 25 . Among different antiviral strategies, host-targeted therapeutics are increasingly recognized as an attractive antiviral treatment approach as they do not exert direct selective pressures on viral pathogens.…”

Feline Coronavirus Antivirals: A Review

“…I-S1–9 and I-S1–16 also significantly inhibited FIPV-I UCD-1 and Black strains and, more surprisingly, the FIPV-II 79-1146 strain, despite the sequence heterogeneity between the spike proteins from FCoV serotype I and II. It was therefore hypothesized that the inhibitory effect may be due to a competition between peptides and viral particles to bind to cell receptors, in a non-serotype-specific manner [ 42 ].…”

Drawing Comparisons between SARS-CoV-2 and the Animal Coronaviruses

“…Neutralization of the polybasic cleavage site of the SARS-CoV-2 S protein with a negatively charged tetrapeptide, GluGluLeuGlu, was shown to lessen the RBD-ACE2 binding strength by 34% [ 144 ]. The antiviral effects of several peptides targeting the S1 domain of FIPV S protein have also been studied, revealing inhibitory effects on virus infection [ 200 ]. In another study, combination of a synthetic peptide FP5 (designed from the putative HR2 domain of the spike protein of FCoV) with interferon-alpha (IFN-α) was found to significantly inhibit FCoV replication in cultured Felis catus whole fetus-4 (fcwf-4) cells [ 201 ].…”