However, its administration appears to induce a variable immune response in the population. new coronavirus shares nearly 80% sequence identity with SARS-CoV-1 [2]. SARS-CoV-2 genome is about 30 kilobases, encoding Barbadin for structural proteins, such as spike (S), membrane (M), envelope (E), Barbadin and nucleocapsid (N) proteins as well as nonstructural proteins (NSPs) [5] (Figure 1). Open in a separate window Figure 1 Interaction between SARS-CoV-2 and host cell. The SARS-CoV-2 virion is composed of 4 structural proteins, spike protein (S), membrane protein (M), envelope protein (E), and nucleocapsid protein (N), associated with single-stranded RNA (ssRNA) of the virion. S protein interacts with the host cell ACE2 protein and is activated by TMPRSS2 as part of the infection mechanism. SARS-CoV-2 can evade the immune system using its NSPs, mainly affecting people with co-morbidities and/or with some type of immunosuppression. NSP1-16 from SARS-CoV-2 are involved in the assembly of viral particles and the viral RNA polymerase [6]. It has been shown that NSP1 from SARS-CoV-1 is an immunosuppressive molecule that inhibits phosphorylation by signal transducer and activator of transcription 1 (STAT1) and hence blocks the interferon (IFN) signaling. Similarly, NSP7 and NSP15 have antagonistic effects on IFN [7]. In addition, mutations in NSP2 and NSP3 have been associated with an increase in the infection capacity of new SARS-CoV-2 variants [6]. Therefore, the IFN response is antagonized by SARS-CoV-2 NSPs, decreasing its levels and contributing to severe infection. Host factors are also important for the development of severe COVID-19. It is relevant to mention that some people develop severe COVID-19, while others remain without symptoms of this disease. Finding differences between asymptomatic and seriously ill patients due to COVID-19 contributes to a broader knowledge of this disease and could help in the development of new therapies. SARS-CoV-2 binds to the angiotensin-converting enzyme type 2 (ACE2) receptor with high affinity through its glycoprotein S (similarly to SARS-CoV-1) [2,8] (Figure 1). ACE2 mRNA is present in all organs [9]. For viral entry, glycoprotein S from SARS-CoV-2 passes from Rabbit polyclonal to SelectinE a pre-fusion to a fusion state by directed cleavage from cathepsin B and L from the endosomal compartment as well as by transmembrane protease serine 2 (TMPRSS2). Primarily, TMPRSS2 plays a critical Barbadin role in pathogenesis and viral spread, and it has been shown that TMPRSS2 inhibitors block the virus entry [10]. Thus, some host genetic factors associated with the development of severe COVID-19 include the polymorphism of (ORF) and are the biggest in the genome. is comprised of two ORFs: (which includes NSP1CNSP11) and (which includes NSP12CNSP16). The second largest protein is the S glycoprotein (gene region. These mutations were found in the third nucleotide for each codon [51]. However, in gene contains the mutation G25566T, which changes AGA (arginine) to ATA (isoleucine). The effect of this mutation is to change a highly polar hydrophilic to a non-polar hydrophobic amino acid. This may alter the folding and function of this protein [23]; however, more studies are necessary to clearly determine the effects of these mutations. One mutation reported for the gene (T28144C) is a synonymous mutation for phenylalanine. This mutation does not modify the folding of the protein; nevertheless, it is suggested that it may help to cloak virus in humans or affect transmission from human to human [23]. However, there are not enough reports to support this proposal. In addition, three important mutations have been detected in NSP13: C17747T, A17858G, and C18060T. It is important to note that this protein is highly conserved in some other viruses, and two of these three mutations are not silent mutations, making them highly interesting to carry out studies and determine their functional importance on virus infectivity. The SARS-CoV-2 has a high contagion rate producing a worldwide spread and a serious health problem [23,50,53,59,60,61]. It was recently reported that there are eight mutations in the SARS-CoV-2 genome that modified the amino acid sequence; such mutations are C1059T, G11083T, C14408T, A23403G, G25563T, G28881A, G28882A, and G28883C. The mutation C14408T in NSP12 was the most prevalent. Furthermore, in ORF3a,.