Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine

Abstract

Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15 140 genome samples collected up to June 1, 2020, we report that SARS-CoV-2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID-19 diagnosis, vaccines, and antibody and small-molecular drugs.

Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors

“…Currently, scientific community are largely focused in the screening of – (i) FDA-approved drug databases, (ii) clinical trials molecules and/or (iii) previously reported coronavirus inhibitors 9 . In silico virtual screening (VS) techniques are proficient to explore CoV protease inhibitors 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 . Yu and co-workers 40 reported the computational screening and findings with regard to potential binding luteolin and other natural compounds against Mpro.…”

“…Vast amount of in silico VS studies against SARS-CoV-2 Mpro has been reported over past months 26-30, 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 . As the detailed description on the molecular modeling studies is out of Scope for this current communication, readers interested in learning more about recent molecular modeling studies to identify probable CoV protease inhibitors are directed to mentioned references 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72...…”

Mutations Strengthened SARS-CoV-2 Infectivity

“…Unfortunately, there are no specific antivirus drugs or effective vaccines developed to moderate this outbreak at present. SARS-CoV-2 has undergone more than 10,000 recorded single mutations compared to the reference genome collected on January 5, 2020 [5,6]. In general, RNA viruses, except for Nidoviruses, are prone to random mutations because of the lack of the exonuclease proofreading activity of the virus-encoded RNA polymerases, RNA viruses.…”

“…Among 725 mutations on SARS-CoV-2 S protein, 89 were on the RBD, which has a total of 194 residues, suggesting that the RBD is subject to more mutations. Our recent studies using over 15,000 genome samples show that SARS-CoV-2 S protein is among the most non-conservative ones in its genome [5]. Since early January 2020, hundreds of new mutations were found on different residue positions of SARS-CoV-2 S protein.…”

Host Immune Response Driving SARS-CoV-2 Evolution

“…The studies of SARS-CoV genomes have, to date, predominantly focused on understanding genome mutation variants, implications in virus transmissions [ 18 , 19 ], and ramifications on the development of diagnostics [ 9 , 20 ], vaccines [ 21 ], antibodies [ 22 ], and drugs [ 21 ]. Although it is difficult to determine the detailed mechanism of every specific mutation, early work on a few initial SARS-CoV-2 strains in Wuhan, China, revealed that hypermutations C > T are most likely resulted from the APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) deamination in RNA editing [ 23 ].…”