COVID-19 is a novel coronavirus with an outbreak of unusual viral pneumonia in Wuhan, China, and then pandemic. Based on its phylogenetic relationships and genomic structures the COVID-19 belongs to genera Betacoronavirus. Human Betacoronaviruses (SARS-CoV-2, SARS-CoV, and MERS-CoV) have many similarities, but also have differences in their genomic and phenotypic structure that can influence their pathogenesis. COVID-19 is containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. A typical CoV contains at least six ORFs in its genome. All the structural and accessory proteins are translated from the sgRNAs of CoVs. Four main structural proteins are encoded by ORFs 10, 11 on the one-third of the genome near the 3′-terminus. The genetic and phenotypic structure of COVID-19 in pathogenesis is important. This article highlights the most important of these features compared to other Betacoronaviruses.
Factors affecting virus pathogenesis
Co-morbidities are cardiovascular and cerebrovascular disease as well as diabetes. Several abnormalities also have been observed including cellular immune deficiency, coagulation activation, myocardia injury, hepatic and kidney injury, and secondary bacterial infection.16 In the majority of cases of severe disease and death, lymphopenia and sustained inflammation have been recorded. Notably, these observations in COVID-19 patients are similar to those who suffered from severe acute respiratory syndrome (SARS) during the 2003 epidemic. There may be a biological mechanism behind this epidemiological anomaly.17
Several kinds of vaccines and antiviral drugs that are based on S protein have been previously evaluated. Du et al. showed vaccines can be based on the S protein include full-length S protein, viral vector, DNA, recombinant S protein and recombinant RBD protein. Considering that, in the in vitro study, antiviral therapies are design based on S protein include RBD–ACE2 blockers, S cleavage inhibitors, fusion core blockers, neutralizing antibodies, protease inhibitors, S protein inhibitors, and small interfering RNAs.18 There are some recombinant compounds such as IFN with ribaverin which has only limited effects against COVID-19 infection.1 The receptor-binding domain of SARS-CoV-2 has a higher affinity for ACE2, while it is a lower affinity for SARS-CoV.1,19 Angiotensin-converting enzyme (ACE) and its homologue ACE2, belongs to the ACE family of dipeptidylcarboxy dipeptidase. However, their physiological functions are varied. On the other hand, ACE2 serves as the binding site for COVID-19. Based on this information, Gurwitz suggested using available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the severity of COVID-19 infections.20 At present therapy is based on identifying and developing monoclonal antibodies that are specific and effective against COVID-19 combines with remdesivir as a novel nucleotide analog prodrug that was used for the treatment of the Ebola virus disease.17,21 To understand the rate of virus spread among people, it is crucial to figure out whether COVID-19 is mutating to improve its binding to human receptors for infection considering its high mutation rate. Any adaptation in the COVID-19 sequence that might make it more efficient at transmitting among people might also boost its virulence.22 The COVID-19 is expected to become less virulent through human to human transmissions due to genetic bottlenecks for RNA viruses often occur during respiratory droplet transmissions.
At present, there is no specific treatment for COVID-19. Given the high rate of transmission of this virus between humans and its pandemics, it is important to identify the basis of its replication, structure, and pathogenicity for discovering a way to the special treatment or the prevention. Due to the high similarity of the virus to its families, efforts have been made to provide medicines and vaccines for COVID-19. Differences in the length of the spike as it is longer in COVID-19 are likely to play an important role in the pathogenesis and treatment of this virus. However, identifying the specific molecular details of the virus is helpful in achieving treatment goals.
Reference & source information: https://www.sciencedirect.com/
Read more on: