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1.
Eur Rev Med Pharmacol Sci ; 25(22): 7162-7184, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1552083

ABSTRACT

The last two decades have witnessed the emergence of three deadly coronaviruses (CoVs) in humans: severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are still no reliable and efficient therapeutics to manage the devastating consequences of these CoVs. Of these, SARS-CoV-2, the cause of the currently ongoing coronavirus disease 2019 (COVID-19) pandemic, has posed great global health concerns. The COVID-19 pandemic has resulted in an unprecedented crisis with devastating socio-economic and health impacts worldwide. This highlights the fact that CoVs continue to evolve and have the genetic flexibility to become highly pathogenic in humans and other mammals. SARS-CoV-2 carries a high genetic homology to the previously identified CoV (SARS-CoV), and the immunological and pathogenic characteristics of SARS-CoV-2, SARS-CoV, and MERS contain key similarities and differences that can guide therapy and management. This review presents salient and updated information on comparative pathology, molecular pathogenicity, immunological features, and genetic characterization of SARS-CoV, MERS-CoV, and SARS-CoV-2; this can help in the design of more effective vaccines and therapeutics for countering these pathogenic CoVs.


Subject(s)
COVID-19/virology , Middle East Respiratory Syndrome Coronavirus/genetics , Pathology, Molecular/methods , SARS Virus/genetics , SARS-CoV-2/genetics , Animals , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/transmission , Female , Global Health/economics , Humans , Male , Mammals , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , SARS Virus/immunology , SARS Virus/pathogenicity , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Virulence
2.
Journal of Applied Pharmaceutical Science ; 11(11):026-033, 2021.
Article in English | Scopus | ID: covidwho-1538775

ABSTRACT

The severity of COVID-19 (coronavirus disease 2019) disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with hyperinflammation induced by excessive release of a range of cytokines and chemokines. Among a plethora of cytokines, interleukin-6 (IL-6) plays a pivotal role in the immunopathology of SARS-CoV-2 infection as IL-6 has been proposed to initiate hypersecretion of cytokines by activating the Janus kinases-signal transducer and activator of transcription (JAK-STAT) pathway. Hence, targeting IL-6 and its receptor can be an appropriate therapeutic strategy to treat SARS-CoV-2 infection. However, tocilizumab (TCZ) is a well-known monoclonal antibody for its anti-inflammatory activities. TCZ has been designed to bind two different IL-6 receptors, viz., membrane-bound and soluble receptors. As an antagonist of IL-6 receptors, TCZ inhibits the JAK-STAT signaling pathway, which is essential for the transcriptional activation of cytokines-producing genes.Hence, the inhibition of IL-6 receptors can substantially reduce hyperinflammation, a key characteristic of severely infected patients with SARS-CoV-2 infection. TCZ has much promise in terms of treating SARS-CoV-2-related hyperinflammation, acute respiratory distress syndrome, and multiple organ damage. Hence, TCZ has been proposed as a potential therapeutic drug for treating COVID-19 disease. However, several discrepancies still exist, such as a well-defined molecular mechanism, efficacy, and safety parameters. In this context, various databases, including Medline, ResearchGate, PubMed, Science Direct, Scopus, and Google Scholar, were explored employing keywords such as “Cytokine storm”, “COVID-19”, “hyper inflammation”, “IL-6”, “TCZ”, and “SARS-COV-2” up to May 2021. The authors independently collected and evaluated research papers for inclusion in the current review, relying on their relatedness to the main theme of the literature review. So, this narrative review aims to provide updated information about the molecular mechanism, efficacy, and safety of TCZ in the treatment of COVID-19. However,several contradictions and challenges associated with TCZ use in the treatment of severely infected patients with COVID-19 have also been discussed. © 2021 Manish Dhawan et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License

3.
Indian Journal of Animal Sciences ; 91(10):791-802, 2021.
Article in English | EMBASE | ID: covidwho-1490189

ABSTRACT

Of the 1,415 human pathogens identified, 175 are responsible for causing emerging diseases, 132 are zoonotic and majority of the diseases are categorized as emerging or re-emerging. Emerging novel Coronavirus (COVID-19) is one of them, and it is responsible for causing social and economically critical disease in both humans and animals. This review presents the understanding of epidemiological characteristics of the COVID-19 pandemic related to host, agent, and the environment with transmission and spread of the disease for better prevention of the COVID-19. The inclination of the viruses to spillover between different species and determining the number of the reservoir of coronaviruses in an entirely new host to create infection is of emerging importance. The understanding of disease patterns will potentiate our expertise to alert how, when, and where the potential epidemic will occur. One health approach involves co-operation from all the sectors, including healthcare (medical and veterinary), environmental, pharmaceutical, educational, research, police, and administration, to combat the COVID-19 pandemic and reduce the public health threat.

4.
Eur Rev Med Pharmacol Sci ; 25(19): 5947-5964, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1478937

ABSTRACT

The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) outbreak has resulted in coronavirus disease 2019 (COVID-19) pandemic worldwide, affecting millions of lives. Although vaccines are presently made available, and vaccination drive is in progress to immunize a larger population; still the risk of SARS-CoV-2 infection and related mortality is persistent amid threats of the third wave of the ongoing pandemic. In the scenario of unavailability of robust and efficient treatment modalities, it becomes essential to understand the mechanism of action of the virus and deeply study the molecular mechanisms (both at the virus level and the host level) underlying the infection processes. Recent studies have shown that coronaviruses (CoVs) cause-specific epigenetic changes in the host cells to create a conducive microenvironment for replicating, assembling, and spreading. Epigenetic mechanisms can contribute to various aspects of the SARS-CoV-2 multiplication cycle, like expressing cytokine genes, viral receptor ACE2, and implicating different histone modifications. For SARS-CoV-2 infection, viral proteins are physically associated with various host proteins resulting in numerous interactions between epigenetic enzymes (i.e., histone deacetylases, bromodomain-containing proteins). The involvement of epigenetic mechanisms in the virus life cycle and the host immune responses to control infection result in epigenetic factors recognized as emerging prognostic COVID-19 biomarkers and epigenetic modulators as robust therapeutic targets to curb COVID-19. Therefore, this narrative review aimed to summarize and discuss the various epigenetic mechanisms that control gene expression and how these mechanisms are altered in the host cells during coronavirus infection. We also discuss the opportunities to exploit these epigenetic changes as therapeutic targets for SARS-CoV-2 infection. Epigenetic alterations and regulation play a pivotal role at various levels of coronavirus infection: entry, replication/transcription, and the process of maturation of viral proteins. Coronaviruses modulate the host epigenome to escape the host immune mechanisms. Therefore, host epigenetic alterations induced by CoVs can be considered to develop targeted therapies for COVID-19.


Subject(s)
COVID-19/genetics , COVID-19/therapy , Coronavirus Infections/genetics , Coronavirus Infections/therapy , Epigenesis, Genetic/genetics , Epigenome , Host-Pathogen Interactions , Humans
5.
Egyptian Journal of Basic and Applied Sciences ; 8(1):261-268, 2021.
Article in English | Scopus | ID: covidwho-1402192

ABSTRACT

The course of the coronavirus disease (COVID-19) pandemic has significantly affected the healthcare systems in multiple ways, the programs of control and the management of patients with other infectious diseases as well as with chronic and acute non-communicable diseases, including those conditions requiring blood transfusions. Blood donations have been decreasing over time in multiple countries with their expected consequences. Although the spread of SARS-CoV-2 has not been detected via blood transfusion, the increasing fear and anxiety among communities have led to a substantial decrease in blood donations. Several research groups have raised concerns about the consequences associated with the scarcity of blood. However, it is critical to understand the underlying causes of the sharp decline in blood donations, as well as the consequences. Hence, we discuss the impact of blood scarcity at the blood banks during the COVID-19 pandemic as well as strategies to promote blood donations, given the experience in some countries with this situation. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

6.
Journal of Experimental Biology and Agricultural Sciences ; 9(3):239-253, 2021.
Article in English | Scopus | ID: covidwho-1328329

ABSTRACT

Although severe acute respiratory syndrome coronavirus – 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) pandemic, is primarily associated with a respiratory infection, it has also been linked to multisystem involvement that includes the digestive tract. Gastrointestinal (GI) manifestations are common in patients with COVID-19 due to the high viral load lodged in the small intestine's mucosa. As a result, it causes an increase in the permeability of the intestinal barrier that favours the passage and translocation of bacteria, from the lumen of the intestine, towards the internal environment, with the appearance of sepsis, with evidence that SARS-CoV-2 has been found in faeces. This article highlights epidemiology, clinical symptoms, and mechanisms related to manifestations of disease in the GI tract and its pathogenesis in patients with COVID-19. It highlights bacterial translocation and COVID-19, mechanisms that control bacterial translocation, intestinal infection and feco-oral transmission, defense mechanisms against microbial invasion, role of microbiota/microbiome and implications of their dysbiosis and alterations during SARS-CoV-2 infection, and lastly protective health benefits by improving dietary habits with nutritional foods approaches amid the ongoing pandemic. Increasing evidence indicates that bacterial translocation appears due to the high viral load of COVID-19 in the mucosa of the GI tract, and the intestinal microbiota contributes to the COVID-19 course owing to their bidirectional relationship with the immune system and lungs. Dysbiosis in gut microbiota leads to increased gut permeability thus predisposing to secondary infection and multiple organ dysfunction. Disruption of intestinal barrier integrity due to dysbiosis may cause translocation of SARS-CoV-2 from lungs into the intestinal lumen via the circulatory and lymphatic system, initiating severe clinical presentation of the infection. A thorough understanding of the key role of gut microbiota, gastrointestinal symptoms, and pathology along with immunomodulatory approaches would help in alleviating morbidity and mortality during the ongoing COVID-19 pandemic. © 2021, Editorial board of Journal of Experimental Biology and Agricultural Sciences.

7.
Infez Med ; 29(2):167-180, 2021.
Article in English | PubMed | ID: covidwho-1248656

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), in a very short span of thirteen months has taken a considerable toll on humanity, resulting in over 3 million deaths with more than 150 million confirmed cases as on May 1, 2021. In the scarcity of a potential antiviral and protective vaccine, COVID-19 has posed high public health concerns, panic, and challenges to limit the spread of this pandemic virus. Only recently have a few vaccine candidates been developed, and vaccination programs have started in some countries. Multiple clinical presentations of COVID-19, animal spillover, cross-species jumping, zoonotic concerns, and emergence of virus variants have altogether created havoc during this ongoing pandemic. Several bodies of research are continuously working to elucidate the exact molecular mechanisms of the pathogenesis. To develop a prospective antiviral therapy/vaccine for SARSCoV-2, it is quite essential to gain insight into the immunobiology and molecular virology of SARS-CoV-2. A thorough literature search was conducted up to 28th February 2021 in the PubMed and other databases for the articles describing the immunopathology and immune response of SARS-CoV-2 infection, which were critically evaluated and used to compile this article to present an overall update. Some of the information was drawn from studies on previous MERS and SARS viruses. Innate as well as adaptive immunity responses are elicited by exposure to SARS-CoV-2. SARS-CoV-2 establishes a successful infection by escaping the host immunity as well as over activating the innate immune mechanisms that result in severe disease outcomes, including cytokine storm. This review summarizes the immunopathology and molecular immune mechanisms elicited during SARS-CoV-2 infection, and their similarities with MERS-CoV and SARS-CoV.

8.
Journal of Applied Pharmaceutical Science ; 11(4):006-013, 2021.
Article in English | Scopus | ID: covidwho-1190605

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the potentially fatal coronavirus disease 2019 (COVID-19), has currently affected over 87 million people with worldwide deaths nearing 1.9 million. Amidst the developing vaccines and effective therapies, there is a need to develop alternative and supportive strategies for ameliorating the effects of SARS-CoV-2 infections in humans and treat COVID-19 patients. Several medicinal plants and herbs contain useful phytochemicals, which are being explored to develop medicines and drugs to counter the COVID-19 pandemic. Withania somnifera is a medicinal herb of growing importance that is extensively utilized in Ayurveda. The medicinal attributes of W. somnifera are owing to a broad range of bioactive secondary metabolites including steroidal lactones [withanone, withanolide D, withanolide A, and withaferin A (WFA)]. Among these, WFA is one of the most interesting naturally occurring bioactive compounds that possess potent anti-tumorigenic, antiinflammatory, pro-apoptotic, anti-angiogenic, and anti-invasive activities. It might bind to SARS-CoV-2 S protein and alter the S protein, thereby hindering its access into the host cells. Withanone and Withanoside V can impede the functional activities of SARS-CoV-2 main protease (Mpro). Withanolides have been found to control cytokine secretions during infection and could alleviate the cytokine storm in the lungs. The combined use of withanolides are several other drugs or therapeutic modalities, such as hydroxychloroquine and dexamethasone, has been demonstrated as an efficient strategy to improve the effectiveness of standard chemotherapy or design a robust therapeutic regime for COVID-19 treatment. Nevertheless, exhaustive research efforts are required to explore the anti-inflammatory and immunomodulatory potentialities of withanolides for alleviating the severity of the disease during SARS-CoV-2 infections. This review highlights the medicinal and therapeutic potential of withanolides against COVID-19. © 2021 Manish Dhawan et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

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