Perceiving SARS-CoV2 Mpro and PLpro dual inhibitors from pool of recognized antiviral compounds of endophytic microbes: an in-silico simulation study

The enormous impact of SARS-CoV2 continues and scientific community is seeking to discover the tactics to impede the spread of virus. The essential result is attenuated, and genetically engineered vaccines are being driven into the market with the general effectiveness being around 80%. Therefore, vaccination is not the sole answer for combat this pandemic. The substitute methodology is adapted to target on this virus with a medication in blend with existing vaccines. Papain like protease (nsp-3; nonstructural protein) and Mpro (nsp-5; nonstructural protein) of novel corona virus are the ideal target to develop drugs as they play different roles that are essential for viral development and replication. Utilizing computational methodology, we plan to distinguish a plausible microbial metabolite as analogue of GRL0617 (the well-established inhibitor of PLpro) and X77 (the well-established inhibitor of Mpro) from the pool of known antiviral compounds of endophytic microbes to interact and inhibit PLpro and Mpro as dual inhibitors. In the wake of collecting known antiviral compounds of endophytic microbes and screened them through pharmacophore hypothesis, molecular docking, and dynamics simulation, we perceive Cytonic acid A and Cytonic acid B to be seen as the potent PLpro and Mpro dual inhibitors using rigorous computational methods.

Autophagy in Viral Development and Progression of Cancer

Autophagy is a complex degradative process by which eukaryotic cells capture cytoplasmic components for subsequent degradation through lysosomal hydrolases. Although this catabolic process can be triggered by a great variety of stimuli, action in cells varies according to cellular context. Autophagy has been previously linked to disease development modulation, including cancer. Autophagy helps suppress cancer cell advancement in tumor transformation early stages, while promoting proliferation and metastasis in advanced settings. Oncoviruses are a particular type of virus that directly contribute to cell transformation and tumor development. Extensive molecular studies have revealed complex ways in which autophagy can suppress or improve oncovirus fitness while still regulating viral replication and determining host cell fate. This review includes recent advances in autophagic cellular function and emphasizes its antagonistic role in cancer cells.

Biochemical and mathematical lessons from the evolution of the SARS-CoV-2 virus: paths for novel antiviral warfare

In the fight against the spread of COVID-19 the emphasis is on vaccination or on reactivating existing drugs used for other purposes. The tight links that necessarily exist between the virus as it multiplies and the metabolism of its host are systematically ignored. Here we show that the metabolism of all cells is coordinated by the availability of a core building block of the cell’s genome, cytidine triphosphate (CTP). This metabolite is also the key to the synthesis of the viral envelope and to the translation of its genome into proteins. This unique role explains why evolution has led to the early emergence in animals of an antiviral immunity enzyme, viperin, that synthesizes a toxic analogue of CTP. The constraints arising from this dependency guide the evolution of the virus. With this in mind, we explored the real-time experiment taking place before our eyes using probabilistic modelling approaches to the molecular evolution of the virus. We have thus followed, almost on a daily basis, the evolution of the composition of the viral genome to link it to the progeny produced over time, particularly in the form of blooms that sparked a firework of viral mutations. Some of those certainly increase the propagation of the virus. This led us to make out the critical role in this evolution of several proteins of the virus, such as its nucleocapsid N, and more generally to begin to understand how the virus ties up the host metabolism to its own benefit. A way for the virus to escape CTP-dependent control in cells would be to infect cells that are not expected to grow, such as neurons. This may account for unexpected body sites of viral development in the present epidemic.

ANTIVIRAL TREATMENT OPTIONS FOR COVID-19 BY REDUCTION OF VIRAL LOAD AND VIRAL SHEDDING

The coronavirus disease 2019 (COVID-19) virus is a public health emergency of international concern, without known effective pharmaceutical treatment so far. It is difficult to treat infected patients who are experiencing acute respiratory failure, liver or cardiac injury, gastroenteritis and many other complications without any drug recommendation. Reducing the viral load is the most important key for Covid-19 treatment, where complication due to infection is highly correlated with the number of viral particles present in the lung and other organs of the patient. Most antivirals are effective against a wide range of viruses, where they inhibit viral development. Some of the possible antiviral treatment options for COVID-19 could be discovered from flu viral treatment that had led to quick respiratory illness recovery through reduction of viral load and viral shedding.

Potential of DNA Intercalating Alkaloids and Other Plant Secondary Metabolites against SARS-CoV-2 Causing COVID-19

Many plants produce secondary metabolites (PSMs) with antiviral activities. Among the antiviral PSMs, lipophilic terpenoids in essential oils can disturb the lipid envelope of viruses. Phenols and polyphenols (flavonoids, rosmarinic acid and tannins) attack viral proteins present in the viral membrane or inside the virus particle. Both phenolics and essential oils are active against free viral particles but not—or to a lesser degree—after a virus has entered a host cell. Another group of PSMs is directed against DNA or RNA. These are DNA intercalators such as sanguinarine, berberine, emetine and other isoquinoline alkaloids, ß-carboline, and quinoline alkaloids such as quinine, cinchonine, dictamine and skimmianine. The DNA intercalators stabilize double-stranded nucleic acids and inhibit the replication, transcription, and translation of genetic material. These alkaloids can inhibit viral development and viral replication in cells, as shown for SARS-CoV-1 and other viruses. Since chloroquine (which is also a DNA intercalator and a chemical derivative of the alkaloid quinine) is apparently clinically helpful against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, it is assumed that intercalating alkaloids, or the medicinal plants producing them, may be interesting candidates for the development of new antiviral drugs for the treatment of coronavirus disease 2019 (COVID-19).

Systemic in Silico Screening in Drug Discovery for Coronavirus Disease (COVID-19) with an Online Interactive Web Server

<p>The emergence of the new coronavirus (nCoV-19) has brought global impact on human health, whilst the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under current adverse situation, we employ virtual screening tools in searching for drugs and nature products which have been already deposited in the DrugBank in attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Besides, we built an interactive online platform (<a href="https://shennongproject.com:11443/#/home">https://shennongproject.com:11443/#/home</a>) for browsing these results with the visual display of small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory works, it may serve not only as the assessment tool for the new drug discovery but also an educational website to meet general interest from the public.</p>

Systemic in Silico Screening in Drug Discovery for Coronavirus Disease (COVID-19) with an Online Interactive Web Server

<p>The emergence of the new coronavirus (nCoV-19) has brought global impact on human health, whilst the interaction between the virus and the host is the foundation of the disease. The viral genome codes a cluster of proteins, each with a unique function in the event of host invasion or viral development. Under current adverse situation, we employ virtual screening tools in searching for drugs and nature products which have been already deposited in the DrugBank in attempt to accelerate the drug discovery process. This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor. Besides, we built an interactive online platform (<a href="https://shennongproject.com:11443/#/home">https://shennongproject.com:11443/#/home</a>) for browsing these results with the visual display of small molecule docked on its potential target protein, without installing any specialized structural software. With continuous maintenance and incorporation of data from laboratory works, it may serve not only as the assessment tool for the new drug discovery but also an educational website to meet general interest from the public.</p>

Entrepreneurship and viral development in rural Western Negev in Israel

Purpose – This paper aims to focus on two main and related issues: evaluating whether the required entrepreneurial capabilities are present according to Gladwell’s law of the few in the Western Negev region of Israel and identifying the economic development model that can generate a viral development. Design/methodology/approach – In this paper, McClelland’s classification was used to evaluate the level of motivation in the region and Gladwell’s law of the few classification was used to understand the potentially positive effect of each entrepreneur on the others and on economic development in general. To evaluate the personal and business capabilities of each entrepreneur, two groups of parameters, one describing the personal profile and the other describing the business behavior of the entrepreneurs, were used. Findings – Most entrepreneurs are ready to cooperate with the open incubator and to contribute to generating common business interest, but mavens and connectors have few of the required personal characteristics and business attitudes. Only the salesmen have the required personal profile, but they lack the necessary business attitude. Highly motivated entrepreneurs, at need-for-power level, have both the required personal profile and business attitude. They are the ones who could generate growth, and a portion of them have the characteristics to become mavens, connectors and salesmen. Practical implications – The willingness to cooperate with a neutral organization and generate common economic interest is present in the Western Negev, but the following actions are required to achieve viral development: persuade and support entrepreneurs at the highest level of motivation to be a part of the few, i.e. mavens, connectors and salesmen; improve the business attitude of mavens, connectors and salesmen; and plan the work program of the open incubator in cooperation with entrepreneurs at the need-for-power level: mavens, connectors and salesmen. Originality/value – Viral economic development can occur if the few mavens, connectors and salesmen in a given sector or region have the required positive personal profile and business attitude, and if most of the entrepreneurs are ready to cooperate with a neutral organization, the open incubator and join efforts with others to generate new common business interests.

Introduction to molecular biology of influenza a viruses.

This minireview presents an overview of current knowledge on virion structure, genome organization and basic events in the development of influenza A virus. The processes of entry, transcription/replication and viral release are described. In this context, the roles of viral proteins (including recently discovered minor polypeptides) in the subsequent stages of viral development are also discussed.