Single-Nucleotide Polymorphisms in Host Pattern-Recognition Receptors Show Association with Antiviral Responses against SARS-CoV-2, in-silico Trial

Coronavirus infectious disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogen-associated molecular patterns (PAMPs) can be detected by host pattern-recognition receptors (PRRs) expressed in inherent immune cells. The polymorphisms in PRRs leads to different recognizing and immune responses against viral infections.

Single-nucleotide polymorphisms of PRRs, minor allele frequency (MAF), and their geographical distribution were obtained from the Ensembl genome database. Interaction between the common polymorphic forms of PRRs (including TLR3, TLR7, RIG-1, and MDA-5) and SARS-CoV-2 virus genome (dsRNA) were predicted using the hybrid protein-RNA docking algorithm HDOCK server. Also, the global distribution of common SNPs and their MAFs were statistically analyzed using SPSS, ver.16.

The wild-type TLR3 and TLR3 SNP rs73873710 had the same docking energy score (-330.48 kcal/mol), and had lower docking energy scores compared to the other two SNPs, rs3775290 and rs3775291 (-301.42 and -295.81 kcal/mol, respectively). TLR7 SNP rs179008 had a higher docking energy score (-423.03 kcal/mol), comparing to the wild-type TLR7 (-445.46 kcal/mol). Also, there was a statistically significant direct relationship between MAF of TLR3 SNP rs3775290 and rs3775291 with SARS-CoV-2 prevalence (P=0.021 and P=0.023, respectively) and prevalence/population ratio of COVID-19 (P=0.026 and P<0.001, respectably).

Wild-type TLR3 and TLR3 SNP rs73873710 can recognize the SARS-CoV-2 dsRNA genome through a better performance compared to TLR3 SNP rs3775290 and TLR3 SNP rs3775291. Therefore, our in-silico study established that PRRs SNPs are associated with antiviral responses against SARS-CoV-2.