Background As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. Results We demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. Conclusions These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.

Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell types and dynamic development of MCOs and validate that these MCOs harbor microglia, astrocytes, neurons, and neural stem/progenitor cells, maturing in a manner that reflects human brain development. We introduce a novel technique for the generation of embryoid bodies (EBs) directly from induced pluripotent stem cells (iPSCs) that involves simplified steps of transitioning directly from 3D cultures as well as orbital shaking culture in a standard 6-well culture plate. This allows for the generation of MCOs with an easy-to-use system that is affordable and accessible by any general lab.

As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. Here, we demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.

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Dear Editor,The COVID-19 vaccines (Pfizer-BNT162b2 and Moderna-mRNA-1273) can elicit an effective immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 1,2 However, titers of elicited serum antibody to spike protein of the virus differ among vaccinated individuals and decline after vaccination. 3,4 Additionally, the ability of the vaccines to protect against newly emerged variants needs to be further elucidated. Therefore, it is important to understand the correlation between levels of vaccination-induced antibody and neutralizing activity against SARS-CoV-2, including the variants.Previous authors have investigated the subject of vaccine efficacy against SARS-CoV-2 variants using both clinical and in-vitro models. For example, a study by Bernal et al. comparing the B.1.617.2 and B.1.1.7 variants using clinical data noted only modest differences in BNT162b2 and ChAdOx1 vaccine's effectiveness. 5 Abu-Raddad et al. used a similar test-negative case-control design and found that the BNT162b2 vaccine's effectiveness was reduced against B.1.351, but noted that protection against severe disease was still robust. 6 An in-vitro study using BNT162b2-elicited serum by Liu et al. reported a roughly equivalent neutralization of B.1.1.7 and P.1 variants when compared to USA-WA1/2020 and slightly lower (but still robust) neutralization for B.1.351. 7 Another in-vitro study by Chen et al. reported reductions in neutralizing activity against B.1.1.7 and B.1.351 variants when examining geometric mean titers (GMTs) using BNT162b2 derived serum. 8 Data from Stamatatos et al. examining the neutralizing ability of sera from 15 donors vaccinated with either Pfizer/BioNTech BNT162b2 or Moderna mRNA-1273 demonstrated that the two mRNA vaccines have reduced potency against divergent variants, specifically B.1.351. 9 In summary, these authors have noted decreased vaccine efficacy against the B.1.351 variant. However, few of these studies included a large cohort of Moderna mRNA-1273 vaccinated donors, and fewer still attempted to compare the neutralizing abil-This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.