ABSTRACT
The COVID-19 pandemic, caused by SARS-CoV-2 - a novel and highly infectious coronavirus, has been spreading around the world for over a year, and poses a serious threat to the public health. Numerous studies have revealed the genome, structure and replication cycle of the SARS-CoV-2 virus as well as the immune response to infection. Data from these studies provide a firm basis for the development of strategies to prevent the further spread of COVID-19, as well as to synthesize effective and safe vaccines and drugs. First and foremost, vaccines are needed to control the COVID-19 pandemic. According to data released by WHO, at the beginning of 2021 there were 63 potential vaccines under clinical examinations, and over 172 in preclinical trials. The most promising vaccines are mRNA-based: Comirnaty (Pfizer- BioNTech), COVID-19 Vaccine (Moderna/NIAID) and CVnCoV (CureVac);vector vaccines: COVID-19 Vaccine (AstraZeneca/Oxford University), Gam-COVIDVac (Gamaleja Institute, Russia) and JNJ-78436735/Ad.26.COV2.S. (Johnson & Johnson), and NVX-CoV2373 recombinant subunit vaccine (Novavax). The following groups of drugs potentially may be used in the COVID-19 therapy: Antiviral drugs with different mechanisms of action - blocking the binding of SARS-CoV-2 to its specific receptor on cell membrane (angiotensin coverting enzyme 2;ACE2) and inhibiting viral entry into host cells (umifenovir, chloroquine, hydroxychloroquine, camostat mesylate and nafamostat);drugs that inhibit viral replication (inhibitors of RNA-dependent RNA polymerase, e.g. remdesivir, favipiravir, ribovirin and molnupiravir;protease inhibitors, e.g. Kaletra);immunomodulating drugs (humanized monoclonal anticytokine antibodies, e.g. adalimumab, infliximab, tocilizumab and anakinra;JAK kinase inhibitors - ruxolitinib and baricitinib), anti-inflammatory drugs (glucocorticosteroids), and neutralizing monoclonal antibodies targeting the SARS-CoV-2 spike protein (S). Moreover, low molecular weight heparin is used for prophylactic and therapeutic purposes. © 2021 Polish Pharmaceutical Society. All rights reserved.
ABSTRACT
In December 2019, a novel highly pathogenic coronavirus SARS-CoV-2, which can be transmitted from person to person, was discovered in patients with infectious respiratory disease in Wuhan, Hubei Province, China. The disease, now known as the 2019 coronavirus disease (COVID-19), has spread rapidly around the world causing a pandemic. This survey presents basic information on the structure and replication cycle of SARS-CoV-2. Fundamental discoveries in genetics and molecular biology of the virus paved the way to design and development of molecules that would act as potential therapeutic agents for COVID-19. The virus belongs to the β-coronavirus 2B lineage. Comparison of the SARS-CoV-2 genome sequence and other available β-coronavirus genomes suggests that it may have evolved naturally from the RaTG13 bat strain of coronaviruses. The virus has a positivesense single-stranded RNA that acts as mRNA following cellular entry and is completely dependent on the translation machinery of the host cell. The genomic RNA of SARS-CoV-2 comprises 14 open reading frames (ORFs). Two main ORFs, ORF1a and ORF1b, encompass two-thirds of the genome and are translated to polyproteins pp1a and pp1ab, respectively. These polyproteins are processed by viral proteases (papain-like protease and chymotrypsin-like protease), to produce 16 nonstructural proteins (Nsp). The remaining one-third of the genome encodes four major structural proteins: Spike (S), membrane (M), envelope (E) and nucleocapsid (N), and seven accessory proteins. SARS-CoV-2 infects human cells by binding to its receptor, i.e. angiotensin converting enzyme 2 (ACE2) at the cell surface through the receptor binding domain of its S protein. Following the entry into the host cell, the genetic material is released into the cytoplasm, and the synthesis of viral proteins necessary for the further process of replication and translation takes place. After mature virus particles are formed, they travel in Golgi vesicles to the host cell membrane where they are released into extracellular space by exocytosis. With the continued spread of SARS-CoV-2 around the world, thousands of mutations have been identified, some of which have relatively high incidences. The following proteins exhibited the highest mutation density: N, S, Nsp2, Nsp3, Nsp5, Nsp6, Nsp7, Nsp12, Nsp13, Orf3 and Orf8. The changes in SARS-CoV-2 proteins caused by mutations can not only affect virus transmission, pathogenesis, and immunogenicity, but also give rise to false negative diagnoses and drug resistance. © 2021 Polish Pharmaceutical Society. All rights reserved.