The Impacts of Antivirals on the Coronavirus Genome Structure and Subsequent Pathogenicity, Virus Fitness and Antiviral Design

• Published in: Biomedicines Vol. 8; no. 10; p. 376
• Main Authors: Lin, Ching-Hung, Yang, Cheng-Yao, Ou, Shan-Chia, Wang, Meilin, Lo, Chen-Yu, Tsai, Tsung-Lin, Wu, Hung-Yi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.09.2020; MDPI
• Subjects: Antiviral agents; antiviral drug; Coronaviridae; coronavirus; Coronaviruses; COVID-19; Disease control; genome structure; Genomes; Innate immunity; Medical importance; Medical treatment; Middle East respiratory syndrome; Mutation; Pathogenicity; remdesivir; Severe acute respiratory syndrome coronavirus 2; Spike protein; Vaccine development; Vaccines; Viruses; United States > US; pathogenicity; innate immunity; antiviral drug; spike protein; coronavirus; genome structure; remdesivir
• DOI: 10.3390/biomedicines8100376
• ISSN: 2227-9059

With the global threat of SARS-CoV-2, much effort has been focused on treatment and disease control. However, how coronaviruses react to the treatments and whether the surviving viruses have altered their characteristics are also unanswered questions with medical importance. To this end, bovine coronavirus (BCoV), which is in the same genus as SARS-CoV-2, was used as a test model and the findings were as follows. With the treatment of antiviral remdesivir, the selected BCoV variant with an altered genome structure developed resistance, but its pathogenicity was not increased in comparison to that of wild type (wt) BCoV. Under the selection pressure of innate immunity, the genome structure was also altered; however, neither resistance developed nor pathogenicity increased for the selected BCoV variant. Furthermore, both selected BCoV variants showed a better efficiency in adapting to alternative host cells than wt BCoV. In addition, the previously unidentified feature that the spike protein was a common target for mutations under different antiviral treatments might pose a problem for vaccine development because spike protein is a common target for antibody and vaccine designs. The findings derived from this fundamental research may contribute to the disease control and treatments against coronaviruses, including SARS-CoV-2.