The CoV disease 2019 (COVID-19) infectious disease outbreak is having a dramatic global effect on public health and the economy. As of October 2020, SARS-CoV-2 has been detected in over 189 countries, has infected over 40 million people, and is responsible for more than 1 million deaths. ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 40 million people worldwide, with over 1 million deaths as of October 2020 and with multiple efforts in the development and testing of antiviral drugs and vaccines under way. In order to gain insights into SARS-CoV-2 evolution and drug targets, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from those of other well-characterized human and animal coronavirus genomes, as well as how polymorphic SARS-CoV-2 genomes are generally. We ultimately sought to identify features in the SARS-CoV-2 genome that may contribute to its viral replication, host pathogenicity, and vulnerabilities. Our analyses suggest the presence of unique sequence signatures in the 3′ untranslated region (3′-UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2 and SARS-CoV as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host-microRNA-mediated interaction between the 3′-UTR and human microRNA hsa-miR-1307-3p based on the results of multiple computational target prediction analyses and an assessment of similar interactions involving the influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3′-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection and the exploitation of conserved features in the 3′-UTR as therapeutic targets warrant further investigation. IMPORTANCE The coronavirus disease 2019 (COVID-19) outbreak is having a dramatic global effect on public health and the economy. As of October 2020, SARS-CoV-2 has been detected in over 189 countries, has infected over 40 million people, and is responsible for more than 1 million deaths. The genome of SARS-CoV-2 is small but complex, and its functions and interactions with human host factors are being studied extensively. The significance of our study is that, using extensive SARS-CoV-2 genome analysis techniques, we identified potential interacting human host microRNA targets that share similarity with those of influenza A virus H1N1. Our study results will allow the development of virus-host interaction models that will enhance our understanding of SARS-CoV-2 pathogenesis and motivate the exploitation of both the interacting viral and host factors as therapeutic targets.
【저자키워드】 COVID-19, SARS-CoV-2, Influenza A H1N1, human microRNA, virus 3′ untranslated region, 【초록키워드】 coronavirus disease, severe acute respiratory syndrome coronavirus 2, public health, Coronavirus disease 2019, Vaccine, coronavirus, Mutation, SARS-CoV, Influenza, Variation, Genome, microRNA, antiviral drugs, Infection, Economy, influenza A virus, Infectious disease, severe acute respiratory syndrome Coronavirus, influenza A, Betacoronavirus, antiviral drug, survival, Viral, Host immune response, outbreak, viral replication, SARS-CoV-2 genome, Lineage, death, CoV, SARS-CoV-2 evolution, target, H1N1, targets, respiratory, pathogenicity, infectious disease outbreak, disease outbreak, disease, SARS-CoV-2 pathogenesis, SARS-CoV-2 replication, mechanism, function, therapeutic targets, Evidence, Interaction, Analysis, Animal coronaviruses, deaths, similarity, therapeutic target, leads, untranslated region, acute respiratory syndrome, Factor, acute respiratory syndrome coronavirus, complex, sequence, effort, human host, H1N1 virus, SARS-CoV-2 genome sequence, SARS-CoV-2 strain, 3′ untranslated region, coronavirus genomes, 3′-UTR, multiple groups, Host, Effect, feature, weakened, ENhance, responsible, identify, conserved, addition, investigated, contribute, unique, analysis, phylogenetically, multiple group, the SARS-CoV-2, the SARS-CoV-2 genome, 【제목키워드】 target, terminal, element, Potential,