The current emergency of the novel coronavirus SARS-CoV2 urged the need for broad-spectrum antiviral drugs as the first line of treatment. Coronaviruses are a large family of viruses that already challenged humanity in at least two other previous outbreaks and are likely to be a constant threat for the future. In this work we developed a pipeline based on in silico docking of known drugs on SARS-CoV1 and 2 RNA-dependent RNA polymerase combined with in vitro antiviral assays on both SARS-CoV2 and the common cold human coronavirus HCoV-OC43. Results showed that certain drugs displayed activity for both viruses at a similar inhibitory concentration, while others were specific. In particular, the antipsychotic drug lurasidone and the antiviral drug elbasvir showed promising activity in the low micromolar range against both viruses with good selectivity index.

Herpesviruses are highly prevalent in the human population, and frequent reactivations occur throughout life. Despite antiviral drugs against herpetic infections, the increasing appearance of drug-resistant viral strains and their adverse effects prompt the research of novel antiherpetic drugs for treating lesions. Peptides obtained from natural sources have recently become of particular interest for antiviral therapy applications. In this work, we investigated the antiviral activity of the peptide A-3302-B, isolated from a marine bacterium, Micromonospora sp., strain MAG 9-7, against herpes simplex virus type 1, type 2, and human cytomegalovirus. Results showed that the peptide exerted a specific inhibitory activity against HSV-2 with an EC50 value of 14 μM. Specific antiviral assays were performed to investigate the mechanism of action of A-3302-B. We demonstrated that the peptide did not affect the expression of viral proteins, but it inhibited the late events of the HSV-2 replicative cycle. In detail, it reduced the cell-to-cell virus spread and the transmission of the extracellular free virus by preventing the egress of HSV-2 progeny from the infected cells. The dual antiviral and previously reported anti-inflammatory activities of A-3302-B, and its effect against an acyclovir-resistant HSV-2 strain are attractive features for developing a therapeutic to reduce the transmission of HSV-2 infections.

Background and objectivesLong lasting immune response to anti-SARS-CoV-2 vaccination in people with Multiple Sclerosis (pwMS) is still largely unexplored. Our study aimed at evaluating the persistence of the elicited amount of neutralizing antibodies (Ab), their activity and T cell response after three doses of anti-SARS-CoV-2 vaccine in pwMS.MethodsWe performed a prospective observational study in pwMS undergoing SARS-CoV-2 mRNA vaccinations. Anti-Region Binding Domain (anti-RBD) of the spike (S) protein immunoglobulin G (IgG) titers were measured by ELISA. The neutralization efficacy of collected sera was measured by SARS-CoV-2 pseudovirion-based neutralization assay. The frequency of Spike-specific IFNγ-producing CD4+ and CD8+ T cells was measured by stimulating Peripheral Blood Mononuclear Cells (PBMCs) with a pool of peptides covering the complete protein coding sequence of the SARS-CoV-2 S.ResultsBlood samples from 70 pwMS (11 untreated pwMS, 11 under dimethyl fumarate, 9 under interferon-γ, 6 under alemtuzumab, 8 under cladribine, 12 under fingolimod and 13 under ocrelizumab) and 24 healthy donors were collected before and up to six months after three vaccine doses. Overall, anti-SARS-CoV-2 mRNA vaccine elicited comparable levels of anti-RBD IgGs, neutralizing activity and anti-S T cell response both in untreated, treated pwMS and HD that last six months after vaccination. An exception was represented by ocrelizumab-treated pwMS that showed reduced levels of IgGs (p<0.0001) and a neutralizing activity under the limit of detection (p<0.001) compared to untreated pwMS. Considering the occurrence of a SARS-CoV-2 infection after vaccination, the Ab neutralizing efficacy (p=0.04), as well as CD4+ (p=0.016) and CD8+ (p=0.04) S-specific T cells, increased in treated COVID+ pwMS compared to uninfected treated pwMS at 6 months after vaccination.DiscussionOur follow-up provides a detailed evaluation of Ab, especially in terms of neutralizing activity, and T cell responses after anti-SARS-CoV-2 vaccination in MS context, over time, considering a wide number of therapies, and eventually breakthrough infection. Altogether, our observations highlight the vaccine response data to current protocols in pwMS and underline the necessity to carefully follow-up anti-CD20- treated patients for higher risk of breakthrough infections. Our study may provide useful information to refine future vaccination strategies in pwMS.

The current emergency of the novel coronavirus SARS-CoV-2 urged the need for broad-spectrum antiviral drugs as the first line of treatment. Coronaviruses are a large family of viruses that already challenged humanity in at least two other previous outbreaks and are likely to be a constant threat for the future. In this work we developed a pipeline based on in silico docking of known drugs on SARS-CoV RNA-dependent RNA polymerase combined with in vitro antiviral assays on both SARS-CoV-2 and the common cold human coronavirus HCoV-OC43. Results showed that certain drugs displayed activity for both viruses at a similar inhibitory concentration, while others were specific. In particular, the antipsychotic drug lurasidone and the antiviral drug elbasvir showed promising activity in the low micromolar range against both viruses with good selective index.

No abstract