The nucleocapsid (N) protein is an important antigen for coronavirus, which participate in RNA package and virus particle release. In this study, we expressed the N protein of SARS-CoV-2 and characterized its biochemical properties. Static light scattering, size exclusive chromatography, and small-angle X-ray scattering (SAXS) showed that the purified N protein is largely a dimer in solution. CD spectra showed that it has a high percentage of disordered region at room temperature while it was best structured at 55 C, suggesting its structural dynamics. Fluorescence polarization assay showed it has non-specific nucleic acid binding capability, which raised a concern in using it as a diagnostic marker. Immunoblot assays confirmed the presence of IgA, IgM and IgG antibodies against N antigen in COVID-19 infection patients' sera, proving the importance of this antigen in host immunity and diagnostics.
Effective, safe, and pharmacokinetically suitable drugs are urgently needed to curb the ongoing COVID-19 pandemic. The main protease or 3C-like protease (Mpro or 3CLpro) of SARS-CoV-2 is considered an important target to formulate potent drugs corresponding to its crucial role in virus replication and maturation in addition to its relatively conserved active site. Promising baseline data on the potency and safety of drugs targeting SARS-CoV-2 Mpro are currently available. However, preclinical and clinical data on the pharmacokinetic profiles of these drugs are very limited. This review discusses the potency, safety, and pharmacokinetic profiles of potential inhibitors of SARS-CoV-2 Mpro and forward directions on the development of future studies focusing on COVID-19 therapeutics.
The 2019–2020 winter was marked by the emergence of a new coronavirus (SARS-CoV-2) related disease (COVID-19), which started in Wuhan, China. Its high human-to-human transmission ability led to a worldwide spread within few weeks and has caused substantial human loss. Mechanical antiviral control approach, drug repositioning, and use of COVID-19 convalescent plasmas (CPs) were the first line strategies utilized to mitigate the viral spread, yet insufficient. The urgent need to contain this deadly pandemic has led searchers and pharmaceutical companies to develop vaccines. However, not all vaccines manufactured are safe. Besides, an alternative and effective treatment option for such an infectious disease would include pure anti-viral neutralizing monoclonal antibodies (NmAbs), which can block the virus at specific molecular targets from entering cells by inhibiting virus-cell structural complex formation, with more safety and efficiency than the CP. Indeed, there is a lot of molecular evidence about the protector effect and the use of molecular feature-based NmAbs as promising therapeutics to contain COVID-19. Thus, from the scientific publication database screening, we here retrieved antibody-related papers and summarized the repertory of characterized NmAbs against SARS-CoV-2, their molecular neutralization mechanisms, and their immunotherapeutic pros and cons. About 500 anti-SARS-CoV-2 NmAbs, characterized through competitive binding assays and neutralization efficacy, were reported at the writing time (January 2021). All NmAbs bind respectively to SARS-CoV-2 S and exhibit high molecular neutralizing effects against wild-type and/or pseudotyped virus. Overall, we defined six NmAb groups blocking SARS-CoV-2 through different molecular neutralization mechanisms, from which five potential neutralization sites on SARS-CoV-2 S protein are described. Therefore, more efforts are needed to develop NmAbs-based cocktails to mitigate COVID-19.
Background: Despite investigating coronavirus among respiratory tract infected cases is a top priority to prevent further transmission, severe acute respiratory syndrome coronavirus 2 positivity among this group of patients remains unexplored in resource-limited settings. Therefore, this study intended to assess the severe acute respiratory syndrome coronavirus 2 positivity among patients presenting with acute respiratory tract infection from 1 July to 31 December 2020 in Harar Region, Ethiopia, from 15 February to 10 March 2021. Methods: A facility-based cross-sectional study design was used. Severe acute respiratory syndrome coronavirus 2 was tested by assaying oropharyngeal swabs using reverse transcriptase–polymerase chain reaction among patients presenting with acute respiratory tract infection in Harari Public Hospitals. A binary logistic regression was used to identify factors associated with severe acute respiratory syndrome coronavirus 2 positivity with an adjusted odds ratio at a 95% confidence interval. Results: Out of a total of 1692 study participants, 388 (22.9%) of them tested positive for severe acute respiratory syndrome coronavirus 2. Of these severe acute respiratory syndrome coronavirus 2 positive patients, 364 (21.6%) patients presented with lower respiratory tract infection, while the rest only 24 (1.4%) presented with upper respiratory tract infection. Independent variables included separated/divorced in marital status (AOR = 0.53, 95% CI: 0.29–0.95), presenting with cough, fever, and difficulty of breathing (AOR = 2.5, 95% CI: 1.22–4.7), age group of 30–39 years (AOR = 0.35, 95% CI: 0.15–0.79), 40–49 years (AOR = 0.37, 95% CI: 0.14–0.94), and 50–59 years (AOR = 0.31, 95% CI: 0.13–0.76) compared to patients with the age of ⩾ 60 years, had statistically significant association with severe acute respiratory syndrome coronavirus 2 positivity. Conclusion: Severe acute respiratory syndrome coronavirus 2 was positive among 388 (22.9%) acute respiratory tract infected people. Elder age, particular symptoms, such as cough, fever, and difficulty of breathing, and married marital status were associated with a severe acute respiratory syndrome coronavirus 2 positive test. In resource-limited setups, where a shortage of testing equipment is common, these findings could contribute to boosting targeted symptom-oriented screening schemes. Moreover, this study could have paramount clinical importance for further studies in the country.
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