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Advantageous variants of the SARS-CoV-2 virus have arisen through mutations, particularly on a single amino acid basis. These point mutations can cause changes in the structure of SARS-CoV-2 and affect the efficiency of interaction with the ACE2 protein. N501Y and E484K mutations affecting binding by ACE2 have been widely observed. This study aimed to predict SARS-CoV-2 mutations that could be as effective as N501Y and E484K and pose a danger due to their high contagiousness. Experimental data on SARS-CoV-2 and ACE2 binding and stability were associated with different amino acid properties and integrated into machine learning and computational biology techniques. As a result of the analyses made in algorithms, N501M, Q414A, N354K, Q498H and N460K have been predicted to be likely to have a dangerous effect. The N501W mutations are most likely to have dangerous effects on the spread of the coronavirus. We suggest that attention should be paid to the position 501 mutation since this position is repeated in the lists of mutations that the algorithm detected as dangerous. G446, G447, Y505, T500, Q493, Y473, and G476 were determined as the positions where dangerous variants could be seen as a result of the analyses of the multiple interaction data created with the ACE2 and RBD interaction data. The 13 dangerous positions and mutations have been detected to accurately describe the position of the mutations caused by the Omicron variant and were among the known dangerous mutations similar to those occurring at Q498, G446, Y505 and Q493 positions. [ABSTRACT FROM AUTHOR]

Coronavirus Disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease, first identified in the Chinese city of Wuhan in November 2019, has since spread worldwide, is the latest human pandemic and has officially infected over 800 million people and has caused nearly seven million deaths to date. Although SARS-CoV-2 belongs to the large family of coronaviruses, it has some unique biological characteristics in its interplay with the human host. Therefore, this narrative review aims to provide an up-to-date overview of the structure of the virus, incubation and shedding in the human host, infectivity and biological evolution over time, as well as the main mechanisms for invading human host cells and replicating within. We also proffer that ongoing epidemiological surveillance of newly emerged variants must always be accompanied by biological studies aimed at deciphering new advantageous traits that may contribute to increasing virulence and pathogenicity, such that the most appropriate strategies for establishing a (relatively) safe coexistence with the human host can be implemented. [ABSTRACT FROM AUTHOR]

In 1918 many countries, but not Spain, were fighting World War I. Spanish press could report about the diffusion and severity of a new infection without censorship for the first-time, so that this pandemic is commonly defined as "Spanish flu", even though Spain was not its place of origin. "Spanish flu" was one of the deadliest pandemics in history and has been frequently compared with the coronavirus disease (COVID)-19 pandemic. These pandemics share similarities, being both caused by highly variable and transmissible respiratory RNA viruses, and diversity, represented by diagnostics, therapies, and especially vaccines, which were made rapidly available for COVID-19, but not for "Spanish flu". Most comparison studies have been carried out in the first period of COVID-19, when these resources were either not yet available or their use had not long started. Conversely, we wanted to analyze the role that the advanced diagnostics, anti-viral agents, including monoclonal antibodies, and innovative COVID-19 vaccines, may have had in the pandemic containment. Early diagnosis, therapies, and anti-COVID-19 vaccines have markedly reduced the pandemic severity and mortality, thus preventing the collapse of the public health services. However, their influence on the reduction of infections and re-infections, thus on the transition from pandemic to endemic condition, appears to be of minor relevance. The high viral variability of influenza and coronavirus may probably be contained by the development of universal vaccines, which are not easy to be obtained. The only effective weapon still remains the disease prevention, to be achieved with the reduction of promiscuity between the animal reservoirs of these zoonotic diseases and humans. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Males are at higher risk relative to females of severe outcomes following COVID-19 infection. Focusing on COVID-19-attributable mortality in the United States (U.S.), we quantified and contrasted years of potential life lost (YPLL) attributable to COVID-19 by sex based on data from the U.S. National Center for Health Statistics as of 31 March 2021, specifically by contrasting male and female percentages of total YPLL with their respective percent population shares and calculating age-adjusted male-to-female YPLL rate ratios, both nationally and for each of the 50 states and the District of Columbia. Using YPLL before age 75 to anchor comparisons between males and females and a novel Monte Carlo simulation procedure to perform estimation and uncertainty quantification, our results reveal a near-universal pattern across states of higher COVID-19-attributable YPLL among males compared to females. Furthermore, the disproportionately high COVID-19 mortality burden among males is generally more pronounced when measuring mortality burden in terms of YPLL compared to death counts, reflecting dual phenomena of males dying from COVID-19 at higher rates and at systematically younger ages relative to females. The U.S. COVID-19 epidemic also offers lessons underscoring the importance of cultivating a public health environment that recognizes sex-specific needs as well as different patterns in risk factors, health behaviors, and responses to interventions between men and women. Public health strategies incorporating focused efforts to increase COVID-19 vaccinations among men are particularly urged. [ABSTRACT FROM AUTHOR]

The coronavirus SARS-CoV-2, which causes Coronavirus disease 2019 (COVID-19), has infected more than 100 million people globally and caused over 2.5 million deaths in just over one year since its discovery in Wuhan, China in December 2019. The pandemic has evoked widespread collateral damage to societies and economies, and has destabilized mental health and well-being. Early in 2020, unprecedented efforts went into the development of vaccines that generate effective antibodies to the SARS-CoV-2 virus. Teams developing twelve candidate vaccines, based on four platforms (messenger RNA, non-replicating viral vector, protein/virus-like particle, and inactivated virus) had initiated or announced the Phase III clinical trial stage by early November 2020, with several having received emergency use authorization in less than a year. Vaccine rollout has proceeded around the globe. Previously, we and others had proposed a target product profile (TPP) for ideal/optimal and acceptable/minimal COVID-19 vaccines. How well do these candidate vaccines stack up to a harmonized TPP? Here, we perform a comparative analysis in several categories of these candidate vaccines based on the latest available trial data and highlight the early successes as well as the hurdles and barriers yet to be overcome for ending the global COVID-19 pandemic. [ABSTRACT FROM AUTHOR]