Immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) using two-dose primary protocol in children and adolescents (Immunita-002, Brazil): A phase IV six-month follow up.

Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health. Objective: The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil. Methods: Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators. Results: The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed. Conclusions: The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.

Synthesis of cannabidiol-based compounds as ACE2 inhibitors with potential application in the treatment of COVID-19.

Cannabis is a general name for plants of the genus Cannabis. Used as fiber, medicine, drug, for religious, therapeutic, and hedonistic purposes along the millenia, it is mostly known for its psychoactive properties. One of its major constituents, cannabidiol (CBD), a non-psychoactive substance, among many other biological activities, has shown potential as an anti-SARS-CoV-2 drug. In this work, three derivatives and an analogue of CBD were synthesized, and cell viability and antiviral activities were evaluated. None of the compounds showed cytotoxicity up to a maximum concentration of 100 µM and, in contrast, displayed a significant antiviral activity, superior to remdesivir and nafamostat mesylate, with IC50 values ranging from 9.4 to 1.9 µM. In order to search for a possible molecular target, the inhibitory activity of the compounds against ACE2 was investigated, with expressive results (IC50 ranging from 3.96 µM to 0.01 µM).

Protease inhibitors from Theobroma cacao impair SARS-CoV-2 replication in vitro.

SARS-CoV-2 is a newly emerging virus from the Coronaviridae family that has already infected over 700 million people worldwide and killed over 6 million. This virus uses protease molecules to replicate and infect the host, which makes these molecules targets for therapeutic substances to eliminate the virus and treat infected people. Through the protein-protein molecular docking approach, we detected two cystatins from Theobroma cacao, TcCYS3 and TcCYS4, described as papain-like protease inhibitors. These inhibitors decreased SARS-CoV-2 genomic copies without toxicity to Vero cells. There is a need to perform comprehensive studies in relevant animal models and to investigate the action mechanisms of protease inhibitors from Theobroma cacao that control the replication of SARS-CoV-2 in human cells.