Molecular characteristics of SARS-CoV-2 Nsp16 protein and analysis of its potential effect on male reproductive function

ABSTRACT

Objective The possibility of coronavirus disease 2019 (COVID-19) involving injury to reproductive function has attracted attention. This study analyzed the genetic characteristics, molecular structure and biological function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Nsp16 protein, and explored potential effects of Nsp16 on germ cells following the virus′ invading testicular tissue, aiming to lay basis for studies of pathogenic mechanisms and therapeutic strategies. Methods Bioinformatic techniques and international biological databases were used to analyze nsp16 genetic variability, Nsp16 spatial structure and function, and effects on genes and proteins of germ cells. DrugBank databases were applied in screening for drugs targeted at Nsp16. Results An evolutionary tree was constructed based on the nsp16 sequences of 30 isolates of 3 coronavirus species. The nsp16 conserved property was 99% amongst SARS-CoV-2 isolates. Nsp16 is a hydrophilic protein, with a 1.9 h half-life inside cells in vitro. Nsp16 has methyltransferase activity, showing potential to regulate gene and functional protein methylation of sperm and Leydig cells. Nsp16 has both linear B cell epitopes and CTL cell epitopes, with capacity to induce immune responses and damage to testicular tissue. Two inhibitory drugs targeted at Nsp16 were found by screening the DrugBank database. Conclusions SARS-CoV-2 Nsp16 is a functional protein encoded by a highly conserved gene, may affect germ cell growth and development by promoting methylation of host cellular genes and proteins following the virus′ invasion into testis tissue through angiotensin-converting enzyme 2 receptors. This report presents Nsp16-targeted chemotherapeutic drugs for the first time, showing high reference value for prevention and treatment of COVID-19 and related lesions of the male reproductive system. © 2021, Publication Centre of Anhui Medical University. All rights reserved.