In Vitro Models for Studying Entry, Tissue Tropism, and Therapeutic Approaches of Highly Pathogenic Coronaviruses.

Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae that contain the largest genome among RNA viruses. Their genome encodes 4 major structural proteins, and among them, the Spike (S) protein plays a crucial role in determining the viral tropism. It mediates viral attachment to the host cell, fusion to the membranes, and cell entry using cellular proteases as activators. Several in vitro models have been developed to study the CoVs entry, pathogenesis, and possible therapeutic approaches. This article is aimed at summarizing the current knowledge about the use of relevant methodologies and cell lines permissive for CoV life cycle studies. The synthesis of this information can be useful for setting up specific experimental procedures. We also discuss different strategies for inhibiting the binding of the S protein to the cell receptors and the fusion process which may offer opportunities for therapeutic intervention.

Cross-reactive memory T cells and herd immunity to SARS-CoV-2.

Immunity is a multifaceted phenomenon. For T cell-mediated memory responses to SARS-CoV-2, it is relevant to consider their impact both on COVID-19 disease severity and on viral spread in a population. Here, we reflect on the immunological and epidemiological aspects and implications of pre-existing cross-reactive immune memory to SARS-CoV-2, which largely originates from previous exposure to circulating common cold coronaviruses. We propose four immunological scenarios for the impact of cross-reactive CD4+ memory T cells on COVID-19 severity and viral transmission. For each scenario, we discuss its implications for the dynamics of herd immunity and on projections of the global impact of SARS-CoV-2 on the human population, and assess its plausibility. In sum, we argue that key potential impacts of cross-reactive T cell memory are already incorporated into epidemiological models based on data of transmission dynamics, particularly with regard to their implications for herd immunity. The implications of immunological processes on other aspects of SARS-CoV-2 epidemiology are worthy of future study.

SARS-CoV-2 infections in children and young people.

Though recent reports link SARS-CoV-2 infections with hyper-inflammatory states in children, most children experience no/mild symptoms, and hospitalization and mortality rates are low in the age group. As symptoms are usually mild and seroconversion occurs at low frequencies, it remains unclear whether children significantly contribute to community transmission. Several hypotheses try to explain age-related differences in disease presentation and severity. Possible reasons for milder presentations in children as compared to adults include frequent contact to seasonal coronaviruses, presence of cross-reactive antibodies, and/or co-clearance with other viruses. Increased expression of ACE2 in young people may facilitate virus infection, while limiting inflammation and reducing the risk of severe disease. Further potential factors include recent vaccinations and a more diverse memory T cell repertoire. This manuscript reviews age-related host factors that may protect children from COVID-19 and complications associated, and addresses the confusion around seropositivity and immunity.

Roles of flavonoids against coronavirus infection.

In terms of public health, the 21st century has been characterized by coronavirus pandemics: in 2002-03 the virus SARS-CoV caused SARS; in 2012 MERS-CoV emerged and in 2019 a new human betacoronavirus strain, called SARS-CoV-2, caused the unprecedented COVID-19 outbreak. During the course of the current epidemic, medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS-CoV-2. Up to now, there is no cure for COVID-19 and waiting for an efficacious vaccine, the development of "savage" protocols, based on "old" anti-inflammatory and anti-viral drugs represents a valid and alternative therapeutic approach. As an alternative or additional therapeutic/preventive option, different in silico and in vitro studies demonstrated that small natural molecules, belonging to polyphenol family, can interfere with various stages of coronavirus entry and replication cycle. Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PLpro, 3CLpro, NTPase/helicase. Due to their pleiotropic activities and lack of systemic toxicity, flavonoids and their derivative may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.

Ten-Year Research Update Review: Antiviral Activities from Marine Organisms.

Oceans cover more than 70 percent of the surface of our planet and are characterized by huge taxonomic and chemical diversity of marine organisms. Several studies have shown that marine organisms produce a variety of compounds, derived from primary or secondary metabolism, which may have antiviral activities. In particular, certain marine metabolites are active towards a plethora of viruses. Multiple mechanisms of action have been found, as well as different targets. This review gives an overview of the marine-derived compounds discovered in the last 10 years. Even if marine organisms produce a wide variety of different compounds, there is only one compound available on the market, Ara-A, and only another one is in phase I clinical trials, named Griffithsin. The recent pandemic emergency caused by SARS-CoV-2, also known as COVID-19, highlights the need to further invest in this field, in order to shed light on marine compound potentiality and discover new drugs from the sea.