The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and more than a million deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. No treatment exists. Epigallocatechin-3-gallate (EGCG), the major component of green tea, has several beneficial properties, including antiviral activities. Therefore, we examined whether EGCG has antiviral activity against SARS-CoV-2. EGCG blocked not only the entry of SARS-CoV-2, but also MERS- and SARS-CoV pseudotyped lentiviral vectors and inhibited virus infections in vitro. Mechanistically, inhibition of the SARS-CoV-2 spike–receptor interaction was observed. Thus, EGCG might be suitable for use as a lead structure to develop more effective anti-COVID-19 drugs.

Highlights Transfusion of sera of convalescent patients is currently in clinical evaluations to treat COVID-19 patients. The level of neutralizing antibodies vary among convalescent patients and fast and simple methods to identify suitable plasma donations are needed. We compared three methods to determine the SARS-CoV-2 neutralizing activity of human convalescent plasma. An ELISA-based sVNT assay required the lowest biosafety level, was fast and sufficient to identify highly neutralizing plasma samples. Weakly neutralizing samples were more reliable detected by the more challenging lentiviral vector based assays or virus neutralization assays.

BackgroundChikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes high fever, rash, and recurrent arthritis in humans. It has efficiently adapted to Aedes albopictus, which also inhabits temperate regions, including Europe and the United States of America. In the past, CHIKV has mainly affected developing countries, but has recently caused large outbreaks in the Caribbean and Latin America. No treatment or licensed CHIKV vaccine exists.Methodology/Principal FindingsHere, we have identified determinants in the CHIKV cell-attachment protein E2 that facilitate cell binding. The extracellular part of the E2 gene is subdivided into the three domains, A, B, and C. These domains were expressed in E. coli and as Fc-fusion proteins generated from HEK293T cells and used for cell-binding assays. Domains A and B bound to all cells tested, independently of their permissiveness to CHIKV infection. Domain C did not bind to cells at all. Furthermore, CHIKV cell entry was promoted by cell-surface glycosaminoglycans (GAGs) and domain B interacted exclusively with GAG-expressing cells. Domain A also bound, although only moderately, to GAG-deficient cells. Soluble GAGs were able to inhibit CHIKV infection up to 90%; however, they enhanced the transduction rate of CHIKV Env pseudotyped vectors in GAG-negative cells.Conclusion/SignificanceThese data imply that CHIKV uses at least two mechanisms to enter cells, one GAG-dependent, via initial attachment through domain B, and the other GAG-independent, via attachment of domain A. These data give indications that CHIKV uses multiple mechanisms to enter cells and shows the potential of GAGs as lead structures for developing antiviral drugs.

Background The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and hundreds of thousands of deaths. The infection causes COVID-19, a disease of the respiratory system of divergent severity. Here, the humoral immune response of a cohort of 143 COVID-19 patients from the University Hospital Frankfurt/Main, Germany was characterized. Methods SARS-CoV-2-specific antibodies were detected by enzyme-linked immunosorbent assay (ELISA). SARS-CoV-2 and hCoV NL63 neutralization activity was analyzed with pseudotyped lentiviral vectors. Results COVID-19 severity increased with age and male patients encountered more serious symptoms than females. Disease severity correlated with the amount of SARS-CoV-2 specific IgG and IgA and the neutralization activity of the antibodies. The amount of SARS-CoV-2 specific IgG antibodies decreased with time after PCR conformation of the infection and antibodies directed against the nucleoprotein waned faster than spike directed antibodies. In contrast, for the common flu coronavirus NL63, COVID19 disease severity seemed to correlate with low NL63-neutralizing activities, suggesting the possibility of cross-reactive protection. Conclusion The results describe the humoral immune responses against SARS-CoV-2 and might aid the identification of correlates of protection needed for vaccine development.

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