The spike (S) protein of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) binds to a host cell receptor which facilitates viral entry. A polybasic motif detected at the cleavage site of ...the S protein has been shown to broaden the cell tropism and transmissibility of the virus. Here we examine the properties of SARS-CoV-2 variants with mutations at the S protein cleavage site that undergo inefficient proteolytic cleavage. Virus variants with S gene mutations generated smaller plaques and exhibited a more limited range of cell tropism compared to the wild-type strain. These alterations were shown to result from their inability to utilize the entry pathway involving direct fusion mediated by the host type II transmembrane serine protease, TMPRSS2. Notably, viruses with S gene mutations emerged rapidly and became the dominant SARS-CoV-2 variants in TMPRSS2-deficient cells including Vero cells. Our study demonstrated that the S protein polybasic cleavage motif is a critical factor underlying SARS-CoV-2 entry and cell tropism. As such, researchers should be alert to the possibility of de novo S gene mutations emerging in tissue-culture propagated virus strains.
The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa
. It has since spread to many countries and is expected to rapidly become dominant worldwide. The ...lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development
, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose.
Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the ...hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.
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•Increasing frequency of SARS-CoV-2 D614G is consistent with a selective advantage•Phylodynamic analyses do not show significantly different growth of D614G clusters•There is no association of D614G replacement with greater severity of infection•The D614G replacement is associated with higher viral loads and younger patient age
Analysis of the spread and frequency of SARS-CoV-2 D614G in the United Kingdom suggests a selective advantage for this strain that is associated with higher viral loads in younger patients but not higher COVID-19 clinical severity or mortality.
Recently a new variant of SARS-CoV-2 was reported from South Africa. World Health Organization (WHO) named this mutant as a variant of concern - Omicron (B.1.1.529) on 26th November 2021. This ...variant exhibited more than thirty amino acid mutations in the spike protein. This mutation rate is exceeding the other variants by approximately 5-11 times in the receptor-binding motif of the spike protein. Omicron (B.1.1.529) variant might have enhanced transmissibility and immune evasion. This new variant can reinfect individuals previously infected with other SARS-CoV-2 variants. Scientists expressed their concern about the efficacy of already existing COVID-19 vaccines against Omicron (B.1.1.529) infections. Some of the crucial mutations that are detected in the receptor-binding domain of the Omicron variant have been shared by previously evolved SARS-CoV-2 variants. Based on the Omicron mutation profile in the receptor-binding domain and motif, it might have collectively enhanced or intermediary infectivity relative to its previous variants. Due to extensive mutations in the spike protein, the Omicron variant might evade the immunity in the vaccinated individuals.
A fast and accurate self-testing tool for COVID-19 diagnosis has become a prerequisite to comprehend the exact number of cases worldwide and to take medical and governmental actions accordingly. ...SARS-CoV-2 (formerly, 2019-nCoV) infection was first reported in Wuhan (China) in December 2019, and then it has rapidly spread around the world, causing ~14 million active cases with ~582,000 deaths as of July 2020. The diagnosis tools available so far have been based on a) viral gene detection, b) human antibody detection, and c) viral antigen detection, among which the viral gene detection by RT-PCR has been found as the most reliable technique. In this report, the current SARS-CoV-2 detection kits, exclusively the ones that were issued an “Emergency Use Authorization” from the U.S. Food and Drug Administration, were discussed. The key structural components of the virus were presented to provide the audience with an understanding of the scientific principles behind the testing tools. The methods that are still in the early research state were also reviewed in a subsection based on the reports available so far.
•The structural biomarkers of SARS-CoV-2 are described.•Viral gene, antigen, and antibody-based detection methods are discussed.•Emergency Use Authorization-issued commercial test kits are explained.•The methods at early research-stage are summarized.
Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these ...antibody responses remain unclear.
Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases.
Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2–specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109).
SARS-CoV-2–specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2–specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2–specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2–specific serum antibody titers showed SARS-CoV-2–specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2–specific IgA titers in nasal fluids were inversely correlated with age.
Systemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2–specific antibodies but may stimulate mucosal SARS-CoV-2–specific IgA secretion.
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