SARS-CoV-2 virus, the causative agent of COVID-19 pandemic, has a genomic organization consisting of 16 nonstructural proteins (nsps), 4 structural proteins, and 9 accessory proteins. Relative of SARS-CoV-2, SARS-CoV, has genomic organization, which is very similar. In this article, the function and structure of the proteins of SARS-CoV-2 and SARS-CoV are described in great detail. The nsps are expressed as a single or two polyproteins, which are then cleaved into individual proteins using two proteases of the virus, a chymotrypsin-like protease and a papain-like protease. The released proteins serve as centers of virus replication and transcription. Some of these nsps modulate the host’s translation and immune systems, while others help the virus evade the host immune system. Some of the nsps help form replication-transcription complex at double-membrane vesicles. Others, including one RNA-dependent RNA polymerase and one exonuclease, help in the polymerization of newly synthesized RNA of the virus and help minimize the mutation rate by proofreading. After synthesis of the viral RNA, it gets capped. The capping consists of adding GMP and a methylation mark, called cap 0 and additionally adding a methyl group to the terminal ribose called cap1. Capping is accomplished with the help of a helicase, which also helps remove a phosphate, two methyltransferases, and a scaffolding factor. Among the structural proteins, S protein forms the receptor of the virus, which latches on the angiotensin-converting enzyme 2 receptor of the host and N protein binds and protects the genomic RNA of the virus. The accessory proteins found in these viruses are small proteins with immune modulatory roles. Besides functions of these proteins, solved X-ray and cryogenic electron microscopy structures related to the function of the proteins along with comparisons to other coronavirus homologs have been described in the article. Finally, the rate of mutation of SARS-CoV-2 residues of the proteome during the 2020 pandemic has been described. Some proteins are mutated more often than other proteins, but the significance of these mutation rates is not fully understood.

Background The DNA end-joining protein, Ku, is essential in non-homologous end joining in prokaryotes and eukaryotes. It was first discovered in eukaryotes and later by PSI blast, in prokaryotes. While Ku in eukaryotes is often a multi-domain protein functioning in DNA repair of physiological and pathological DNA double-stranded breaks, Ku in prokaryotes is a single-domain protein functioning in pathological DNA repair in spores or late stationary phase. In this paper, we have attempted to systematically search for Ku protein in different phyla of bacteria and archaea as well as in different groups of eukarya. Result From our search of 122 sequenced bacterial genomes using NCBI BLASTP, only 31 genomes yielded at least one Ku sequence. In eukarya, we found Ku protein in 27 out of 59 species using BLASTP in NCBI. Since the entire genome of all eukaryotic species is not fully sequenced this number could go up. From a comprehensive search of all OrthoDB archaeal genomes, we received a positive hit in 19 specific archaeal species that possessed Ku70/80 beta-barrel domain. Likewise, we retrieved 11 viral sequences consisting of the Ku70/80 beta-barrel domain using a comprehensive search against virus genomes in OrthoDB. We then drew a phylogenetic maximum likelihood tree to determine the ancestral relationship between Ku70 and Ku80 in eukaryotes and Ku in bacteria, archaea, and viruses. Our tree revealed a common node for some Ku, Ku70, and Ku80. Among the three forms of Ku, Ku70 showed the highest sequence divergence. Conclusion One model proposed for Ku evolution hypothesizes that Ku70 arose first and duplicated to form Ku80. Ku70 or Ku80 horizontally transferred onto archaea and then onto bacteria to give the present forms of Ku in three domains of life. Additionally, we analyzed the domains of the different eukaryotic species to demonstrate that fusion, terminal addition, terminal deletion, single domain loss, and single domain emergence events during evolution.

Background The DNA end joining protein, Ku, is essential in Non-Homologous End Joining in prokaryotes and eukaryotes. It was first discovered in eukaryotes and later by PSI blast, was discovered in prokaryotes. While Ku in eukaryotes is often a multi domain protein functioning in DNA repair of physiological and pathological DNA double stranded breaks, Ku in prokaryotes is a single domain protein functioning in pathological DNA repair in spores or late stationary phase. In this paper we have attempted to systematically search for Ku protein in different phyla of bacteria and archaea as well as in different kingdoms of eukarya. Result From our search of 116 sequenced bacterial genomes, only 25 genomes yielded at least one Ku sequence. From a comprehensive search of all NCBI archaeal genomes, we received a positive hit in 7 specific archaea that possessed Ku. In eukarya, we found Ku protein in 27 out of 59 species. Since the entire genome of all eukaryotic species is not fully sequenced this number could go up. We then drew a phylogenetic maximum likelihood tree to determine the ancestral relationship between Ku70 and Ku80 in eukaryotes and Ku in prokaryotes. Out tree revealed a common node for some archaeal Ku, Ku70 and Ku80. Conclusion This led us to hypothesize that Ku from archaea transferred through horizontal gene transfer onto neozoa and then duplicated to form Ku70 and Ku80. Additionally, we analyzed the domains of the different eukaryotic species to demonstrate that fusion, fission, terminal addition, terminal deletion, single domain loss, single domain emergence events during evolution.