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1.
Int J Mol Sci ; 23(21)2022 Nov 05.
Article in English | MEDLINE | ID: covidwho-2099579

ABSTRACT

Several human diseases are caused by viruses, including cancer, Type I diabetes, Alzheimer's disease, and hepatocellular carcinoma. In the past, people have suffered greatly from viral diseases such as polio, mumps, measles, dengue fever, SARS, MERS, AIDS, chikungunya fever, encephalitis, and influenza. Recently, COVID-19 has become a pandemic in most parts of the world. Although vaccines are available to fight the infection, their safety and clinical trial data are still questionable. Social distancing, isolation, the use of sanitizer, and personal productive strategies have been implemented to prevent the spread of the virus. Moreover, the search for a potential therapeutic molecule is ongoing. Based on experiences with outbreaks of SARS and MERS, many research studies reveal the potential of medicinal herbs/plants or chemical compounds extracted from them to counteract the effects of these viral diseases. COVID-19's current status includes a decrease in infection rates as a result of large-scale vaccination program implementation by several countries. But it is still very close and needs to boost people's natural immunity in a cost-effective way through phytomedicines because many underdeveloped countries do not have their own vaccination facilities. In this article, phytomedicines as plant parts or plant-derived metabolites that can affect the entry of a virus or its infectiousness inside hosts are described. Finally, it is concluded that the therapeutic potential of medicinal plants must be analyzed and evaluated entirely in the control of COVID-19 in cases of uncontrollable SARS infection.


Subject(s)
COVID-19 , Plants, Medicinal , Virus Diseases , Humans , COVID-19/drug therapy , COVID-19/epidemiology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Antiviral Agents/chemistry , SARS-CoV-2 , Disease Outbreaks/prevention & control , Virus Diseases/drug therapy , Plants, Medicinal/metabolism
2.
Infect Dis Clin North Am ; 36(4): 897-909, 2022 12.
Article in English | MEDLINE | ID: covidwho-2095435

ABSTRACT

Procalcitonin is a commonly used biomarker for infection and severity in the intensive care unit. Although relatively specific for bacterial, as opposed to viral, infections, serum procalcitonin levels also correlate with disease severity and thus cannot reliably distinguish between bacterial and nonbacterial infections in the setting of critical illness, particularly in cases of severe influenza and coronavirus disease-2019. Baseline procalcitonin levels are insufficiently discriminative to permit the withholding of antibiotics in patients with critical illness and suspected sepsis. Trends in procalcitonin levels over time, however, give us the opportunity to individualize the duration of antibiotics without negative impacts on mortality.


Subject(s)
Bacterial Infections , COVID-19 , Sepsis , Virus Diseases , Humans , Procalcitonin , Critical Illness , Critical Care , Biomarkers , Sepsis/diagnosis , Sepsis/drug therapy , Anti-Bacterial Agents/therapeutic use , Virus Diseases/drug therapy , Bacterial Infections/drug therapy
3.
Biomed Pharmacother ; 156: 113850, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2085961

ABSTRACT

As diseases caused by new and emerging viruses continue to be a major threat to humans and animals worldwide the need for new therapeutic options intensifies. A wide variety of viruses including Influenza A virus, Human immunodeficiency virus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus require ion channels for efficient replication. Thus, targeting host ion channels may serve as an effective means to attenuate virus replication and help treat viral diseases. Targeting host ion channels is an attractive therapeutic option because a range of ion channel-blocking compounds already exist for the treatment of other human diseases and some of these possess in vitro and sometimes in vivo antiviral activity. Therefore, identifying the specific ion channels involved in replicative cycles could provide opportunities to repurpose these ion channel inhibitors for treating viral diseases. Furthermore, optimised methodologies for identifying effective ion channel targeting drugs and their mechanisms of action could enable rapid responses to newly emerged viruses. This review discusses the potential of ion channels as suitable drug targets to treat diseases caused by viruses by describing known ion channel targeting drugs including their antiviral activity; by summarising prior research demonstrating the requirement for host ion channels for efficient replication of some viruses; and by hypothesising about the role these drugs might play in our ongoing fight against viral diseases.


Subject(s)
Drug Repositioning , Virus Diseases , Animals , Humans , Virus Replication , Virus Diseases/drug therapy , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Ion Channels
4.
BMC Med ; 20(1): 359, 2022 10 21.
Article in English | MEDLINE | ID: covidwho-2079420

ABSTRACT

BACKGROUND: The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5-30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. METHODS: The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. RESULTS: Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. CONCLUSIONS: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.


Subject(s)
Anidulafungin , Bunyaviridae Infections , Virus Diseases , Animals , Mice , Anidulafungin/pharmacology , Anidulafungin/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Bunyaviridae Infections/drug therapy , Clathrin , Receptor, Interferon alpha-beta , SARS-CoV-2 , Viral Proteins , Virus Diseases/drug therapy
5.
Pharmacol Ther ; 237: 108249, 2022 09.
Article in English | MEDLINE | ID: covidwho-2015917

ABSTRACT

Fine control over chloride homeostasis in the lung is required to maintain membrane excitability, transepithelial transport as well as intra- and extracellular ion and water homeostasis. Over the last decades, a growing number of chloride channels and transporters have been identified in the cells of the pulmonary vasculature and the respiratory tract. The importance of these proteins is underpinned by the fact that impairment of their physiological function is associated with functional dysregulation, structural remodeling, or hereditary diseases of the lung. This paper reviews the field of chloride channels and transporters in the lung and discusses chloride channels in disease processes such as viral infections including SARS-CoV- 2, pulmonary arterial hypertension, cystic fibrosis and asthma. Although chloride channels have become a hot research topic in recent years, remarkably few of them have been targeted by pharmacological agents. As such, we complement the putative pathophysiological role of chloride channels here with a summary of their therapeutic potential.


Subject(s)
Cystic Fibrosis , Pulmonary Arterial Hypertension , Virus Diseases , Chloride Channels/metabolism , Chlorides/metabolism , Cystic Fibrosis/drug therapy , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Familial Primary Pulmonary Hypertension , Humans , Lung/metabolism , Virus Diseases/drug therapy
6.
Appl Microbiol Biotechnol ; 106(18): 5863-5877, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2007131

ABSTRACT

This mini review focuses on the diagnosis and treatment of virus diseases using Crisper-Cas technology. The present paper describes various strategies involved in diagnosing diseases using Crispr-Cas-based assays. Additionally, CRISPR-Cas systems offer great potential as new therapeutic tools for treating viral infections including HIV, Influenza, and SARS-CoV-2. There are several major challenges to be overcome before this technology can be applied routinely in clinical settings, such as finding a suitable delivery tool, toxicity, and immunogenicity, as well as off-target effects. This review also discusses ways to deal with the challenges associated with Crisper-Cas technology. KEY POINTS: • Crisper technology is being applied to diagnose infectious and non-infectious diseases. • A new generation of CRISPR-Cas-based assays has been developed which detect pathogens within minutes, providing rapid diagnosis of diseases. • Crispr-Cas tools can be used to combat viral infections, specifically HIV, influenza, and SARS-CoV-2.


Subject(s)
COVID-19 , HIV Infections , Influenza, Human , Virus Diseases , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Testing , CRISPR-Cas Systems , HIV Infections/diagnosis , HIV Infections/drug therapy , Humans , Influenza, Human/diagnosis , Influenza, Human/drug therapy , SARS-CoV-2/genetics , Virus Diseases/diagnosis , Virus Diseases/drug therapy
7.
Cell ; 185(13): 2210-2212, 2022 06 23.
Article in English | MEDLINE | ID: covidwho-1936136

ABSTRACT

Many approved drugs, including antivirals, are small-molecule inhibitors of disease-causing proteins. Such inhibitors often elicit resistance during treatment. Chaturvedi et al. propose new, feedback-disruptor (FD) antivirals that efficiently cure infected cells from viruses and minimize the chance of resistance, providing a new paradigm to treat viral infections and possibly other diseases.


Subject(s)
Antiviral Agents , Virus Diseases , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Feedback , Humans , Virus Diseases/drug therapy
8.
Phytother Res ; 35(11): 6148-6169, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1935724

ABSTRACT

Uncontrolled inflammatory responses or cytokine storm associated with viral infections results in deleterious consequences such as vascular leakage, severe hemorrhage, shock, immune paralysis, multi-organ failure, and even death. With the emerging new viral infections and lack of effective prophylactic vaccines, evidence-based complementary strategies that limit viral infection-mediated hyperinflammatory responses could be a promising approach to limit host tissue injury. The present review emphasizes the potentials of antiinflammatory phytochemicals in limiting hyperinflammatory injury caused by viral infections. The predominant phytochemicals along with their mechanism in limiting hyperimmune and pro-inflammatory responses under viral infection have been reviewed comprehensively. How certain phytochemicals can be effective in limiting hyper-inflammatory response indirectly by favorably modulating gut microbiota and maintaining a functional intestinal barrier has also been presented. Finally, we have discussed improved systemic bioavailability of phytochemicals, efficient delivery strategies, and safety measures for effective antiinflammatory phytotherapies, in addition to emphasizing the requirement of tightly controlled clinical studies to establish the antiinflammatory efficacy of the phytochemicals. Collectively, the review provides a scooping overview on the potentials of bioactive phytochemicals to mitigate pro-inflammatory injury associated with viral infections.


Subject(s)
Phytochemicals , Virus Diseases , Anti-Inflammatory Agents/pharmacology , Humans , Intestines , Phytochemicals/pharmacology , Phytotherapy , Virus Diseases/drug therapy , Virus Diseases/prevention & control
9.
Cell Chem Biol ; 29(7): 1113-1125.e6, 2022 07 21.
Article in English | MEDLINE | ID: covidwho-1894864

ABSTRACT

The increasingly frequent outbreaks of pathogenic viruses have underlined the urgent need to improve our arsenal of antivirals that can be deployed for future pandemics. Innate immunity is a powerful first line of defense against pathogens, and compounds that boost the innate response have high potential to act as broad-spectrum antivirals. Here, we harnessed localization-dependent protein-complementation assays (called Alpha Centauri) to measure the nuclear translocation of interferon regulatory factors (IRFs), thus providing a readout of innate immune activation following viral infection that is applicable to high-throughput screening of immunomodulatory molecules. As proof of concept, we screened a library of kinase inhibitors on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and identified Gilteritinib as a powerful enhancer of innate responses to viral infection. This immunostimulatory activity of Gilteritinib was found to be dependent on the AXL-IRF7 axis and results in a broad and potent antiviral activity against unrelated RNA viruses.


Subject(s)
COVID-19 , Virus Diseases , Antiviral Agents/pharmacology , Humans , Immunity, Innate , SARS-CoV-2 , Virus Diseases/drug therapy
10.
Int J Mol Sci ; 23(12)2022 Jun 12.
Article in English | MEDLINE | ID: covidwho-1887212

ABSTRACT

The majority of transcribed RNAs do not codify for proteins, nevertheless they display crucial regulatory functions by affecting the cellular protein expression profile. MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) are effectors of interfering mechanisms, so that their biogenesis is a tightly regulated process. Onconase (ONC) is an amphibian ribonuclease known for cytotoxicity against tumors and antiviral activity. Additionally, ONC administration in patients resulted in clinical effectiveness and in a well-tolerated feature, at least for lung carcinoma and malignant mesothelioma. Moreover, the ONC therapeutic effects are actually potentiated by cotreatment with many conventional antitumor drugs. This review not only aims to describe the ONC activity occurring either in different tumors or in viral infections but also to analyze the molecular mechanisms underlying ONC pleiotropic and cellular-specific effects. In cancer, data suggest that ONC affects malignant phenotypes by generating tRNA fragments and miRNAs able to downregulate oncogenes expression and upregulate tumor-suppressor proteins. In cells infected by viruses, ONC hampers viral spread by digesting the primer tRNAs necessary for viral DNA replication. In this scenario, new therapeutic tools might be developed by exploiting the action of ONC-elicited RNA derivatives.


Subject(s)
Antineoplastic Agents , MicroRNAs , Neoplasms , Virus Diseases , Antineoplastic Agents/metabolism , Cell Line, Tumor , DNA Replication , DNA, Viral , Humans , MicroRNAs/genetics , Neoplasms/drug therapy , Neoplasms/genetics , RNA, Transfer/genetics , Ribonucleases/genetics , Ribonucleases/metabolism , Virus Diseases/drug therapy , Virus Diseases/genetics , Virus Replication
11.
Viruses ; 14(5)2022 04 28.
Article in English | MEDLINE | ID: covidwho-1820410

ABSTRACT

New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many acute-infectious viruses. DHODH is a rate-limiting enzyme catalyzing the fourth step in de novo pyrimidine synthesis. Therefore, it has also been developed as a therapeutic target for many diseases relying on cellular pyrimidine resources, such as cancers, autoimmune diseases, and viral or bacterial infections. Significantly, the successful use of DHODH inhibitors (DHODHi) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection further supports the application prospects. This review focuses on the advantages of HTAs and the antiviral effects of DHODHi with clinical applications. The multiple functions of DHODHi in inhibiting viral replication, stimulating ISGs expression, and suppressing cytokine storms make DHODHi a potent strategy against viral infection.


Subject(s)
COVID-19 , Dihydroorotate Dehydrogenase , Virus Diseases , Viruses , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Dihydroorotate Dehydrogenase/antagonists & inhibitors , Humans , Pyrimidines , SARS-CoV-2/drug effects , Virus Diseases/drug therapy , Virus Replication/drug effects , Viruses/drug effects
12.
Expert Opin Ther Pat ; 32(7): 791-815, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1795496

ABSTRACT

INTRODUCTION: Several viral infections cause life-threatening consequences in humans, making them the most serious public health concerns. Despite the fact that several antiviral medicines are available on the market, there is no full treatment for many important viral infections. To date, antiviral medicines have significantly reduced the spread of epidemics, but their continued use has resulted in the creation of drug-resistant variants throughout time. As a result, the development of new, safe, and efficient antiviral drugs is critical. AREAS COVERED: This review covered reports in the patent literature in the period 2014 to the first quarter of 2021 on the antiviral activities of thiazole derivatives. These molecules were reported to inhibit a wide range of viruses including influenza viruses, coronaviruses, herpes viruses, hepatitis B and C, bovine viral diarrhea virus, chikungunya virus and human immunodeficiency viruses. EXPERT OPINION: The most bioactive molecules can be used as lead structures for the development of new thiazole compounds with potent and selective antiviral activity. In addition, more efforts are needed to better understand the host-virus interactions for the discovery and development of new therapeutic agents and creative treatment strategies that are supposed to improve rates of clinical cure of the serious viruses.


Subject(s)
Thiazoles , Virus Diseases , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Patents as Topic , Thiazoles/chemistry , Thiazoles/pharmacology , Thiazoles/therapeutic use , Virus Diseases/drug therapy
13.
Molecules ; 27(9)2022 Apr 19.
Article in English | MEDLINE | ID: covidwho-1792595

ABSTRACT

The marine environment presents a favorable avenue for potential therapeutic agents as a reservoir of new bioactive natural products. Due to their numerous potential pharmacological effects, marine-derived natural products-particularly marine peptides-have gained considerable attention. These peptides have shown a broad spectrum of biological functions, such as antimicrobial, antiviral, cytotoxic, immunomodulatory, and analgesic effects. The emergence of new virus strains and viral resistance leads to continuing efforts to develop more effective antiviral drugs. Interestingly, antimicrobial peptides (AMPs) that possess antiviral properties and are alternatively regarded as antiviral peptides (AVPs) demonstrate vast potential as alternative peptide-based drug candidates available for viral infection treatments. Hence, AVPs obtained from various marine organisms have been evaluated. This brief review features recent updates of marine-derived AVPs from 2011 to 2021. Moreover, the biosynthesis of this class of compounds and their possible mechanisms of action are also discussed. Selected peptides from various marine organisms possessing antiviral activities against important human viruses-such as human immunodeficiency viruses, herpes simplex viruses, influenza viruses, hepatitis C virus, and coronaviruses-are highlighted herein.


Subject(s)
Biological Products , Virus Diseases , Viruses , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Biological Products/pharmacology , Biological Products/therapeutic use , Humans , Peptides/pharmacology , Peptides/therapeutic use , Virus Diseases/drug therapy
14.
PLoS Pathog ; 18(3): e1010366, 2022 03.
Article in English | MEDLINE | ID: covidwho-1793485

ABSTRACT

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses. Mechanistically, QUIN induced the production of type I interferon (IFN-I) via activating the N-methyl-d-aspartate receptor (NMDAR) and Ca2+ influx to activate Calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). Importantly, QUIN treatment effectively inhibited viral infections and alleviated disease progression in mice. Furthermore, kmo-/- mice were vulnerable to pathogenic viral challenge with severe clinical symptoms. Collectively, our results demonstrated that KMO and its enzymatic product QUIN were potential therapeutics against emerging pathogenic viruses.


Subject(s)
Kynurenine 3-Monooxygenase , Virus Diseases , Animals , Calcium/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Interferon Regulatory Factor-3/metabolism , Kynurenine/metabolism , Kynurenine 3-Monooxygenase/metabolism , Mice , Quinolinic Acid/metabolism , Quinolinic Acid/pharmacology , Virus Diseases/drug therapy
15.
Adv Exp Med Biol ; 1366: 137-153, 2022.
Article in English | MEDLINE | ID: covidwho-1782744

ABSTRACT

With the increasing global human population, travel, and socioeconomic activities, more and more novel pathogenic viruses will emerge or re-emerge. While more than 260 viruses are known to infect humans, only a small minority of these viral diseases are treatable by clinically approved antiviral drugs. Apart from these identified viruses, new emerging viruses and drug-resistant viruses are also important challenges to our public health and healthcare systems. The COVID-19 and influenza pandemics remind us the importance of getting broad-spectrum antivirals against emerging and re-emerging respiratory viruses. Broad-spectrum antivirals against different viral families for fighting the currently known viruses and novel emerging viruses are urgently needed. Viral entry is the universal first step for viral infection, and therefore is a promising target for identifying broad-spectrum antivirals. In this chapter, we mainly focus on discussing the risks of respiratory viruses, the challenge of finding broad-spectrum antivirals, the entry processes of respiratory viruses, the current studies on broad-spectrum entry inhibitors for respiratory viruses, and the directions for discovering broad-spectrum antivirals in the future.


Subject(s)
COVID-19 , Virus Diseases , Viruses , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Virus Diseases/drug therapy , Virus Internalization
16.
Molecules ; 27(7)2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1776292

ABSTRACT

Nitric oxide is a ubiquitous signaling radical that influences critical body functions. Its importance in the cardiovascular system and the innate immune response to bacterial and viral infections has been extensively investigated. The overproduction of NO is an early component of viral infections, including those affecting the respiratory tract. The production of high levels of NO is due to the overexpression of NO biosynthesis by inducible NO synthase (iNOS), which is involved in viral clearance. The development of NO-based antiviral therapies, particularly gaseous NO inhalation and NO-donors, has proven to be an excellent antiviral therapeutic strategy. The aim of this review is to systematically examine the multiple research studies that have been carried out to elucidate the role of NO in viral infections and to comprehensively describe the NO-based antiviral strategies that have been developed thus far. Particular attention has been paid to the potential mechanisms of NO and its clinical use in the prevention and therapy of COVID-19.


Subject(s)
COVID-19 , Virus Diseases , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Immunity, Innate , Nitric Oxide , Nitric Oxide Synthase Type II/metabolism , Virus Diseases/drug therapy
17.
Genet Res (Camb) ; 2021: 9952620, 2021.
Article in English | MEDLINE | ID: covidwho-1775004

ABSTRACT

Purpose: Herbal medicine is one of crucial symbols of Chinese national medicine. Investigation on molecular responses of different herbal strategies against viral myocarditis is immeasurably conducive to targeting drug development in the current international absence of miracle treatment. Methods: Literature retrieval platforms were applied in the collection of existing empirical evidences for viral myocarditis-related single-herbal strategies. SwissTargetPrediction, Metascape, and Discovery Studio coordinating with multidatabases investigated underlying target genes, interactive proteins, and docking molecules in turn. Results: Six single-herbal medicines consisting of Huangqi (Hedysarum Multijugum Maxim), Yuganzi (Phyllanthi Fructus), Kushen (Sophorae Flavescentis Radix), Jianghuang (Curcumaelongae Rhizoma), Chaihu (Radix Bupleuri), and Jixueteng (Spatholobus Suberectus Dunn) meet the requirement. There were 11 overlapped and 73 unique natural components detected in these herbs. SLC6A2, SLC6A4, NOS2, PPARA, PPARG, ACHE, CYP2C19, CYP51A1, and CHRM2 were equally targeted by six herbs and identified as viral myocarditis-associated symbols. MCODE algorithm exposed the hub role of SRC and EGFR in strategies without Jianghuang. Subsequently, we learned intermolecular interactions of herbal components and their targeting heart-tissue-specific CHRM2, FABP3, TNNC1, TNNI3, TNNT2, and SCN5A and cardiac-myocytes-specific IL6, MMP1, and PLAT coupled with viral myocarditis. Ten interactive characteristics such as π-alkyl and van der Waals were modeled in which ARG111, LYS253, ILE114, and VAL11 on cardiac troponin (TNNC1-TNNI3-TNNT2) and ARG208, ASN106, and ALA258 on MMP1 fulfilled potential communicating anchor with ellagic acid, 5α, 9α-dihydroxymatrine, and leachianone g via hydrogen bond and hydrophobic interaction, respectively. Conclusions: The comprehensive outcomes uncover differences and linkages between six herbs against viral myocarditis through component and target analysis, fostering development of drugs.


Subject(s)
Cardiovascular Infections , Drugs, Chinese Herbal , Myocarditis , Plants, Medicinal , Virus Diseases , Drugs, Chinese Herbal/therapeutic use , Humans , Myocarditis/drug therapy , Phytotherapy , Serotonin Plasma Membrane Transport Proteins , Virus Diseases/drug therapy
18.
J Med Virol ; 94(7): 2962-2968, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1739192

ABSTRACT

Cyclin-dependent kinases (CDKs) are protein kinases that play a key role in cell division and transcriptional regulation. Recent studies have demonstrated the critical roles of CDKs in various viral infections. However, the molecular processes underpinning CDKs' roles in viral infection and host antiviral defense are unknown. This minireview briefly overviews CDKs' functions and highlights the most recent discoveries of CDKs' emerging roles during viral infections, thereby providing a scientific and theoretical foundation for antiviral regulation and shedding light on developing novel drug targets and therapeutic strategies against viral infection.


Subject(s)
COVID-19 , Virus Diseases , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cyclin-Dependent Kinases/metabolism , Cyclin-Dependent Kinases/therapeutic use , Humans , SARS-CoV-2 , Virus Diseases/drug therapy
19.
Science ; 375(6585): 1133-1139, 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1736002

ABSTRACT

The vaccine and drug discovery responses to COVID-19 have worked far better than could have been imagined. Yet by the end of 2021, more than 5 million people had died, and the pandemic continues to evolve and rage globally. This Review will describe how each of the vaccines, antibody therapies, and antiviral drugs that have been approved to date were built on decades of investment in technology and basic science. We will caution that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has so far proven a straightforward test of our pandemic preparedness, and we will recommend steps we should undertake now to prepare for, to minimize the effects of, and ideally to prevent future pandemics. Other Reviews in this series describe the interactions of SARS-CoV-2 with the immune system and those therapies that target the host response to infection.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Vaccines , COVID-19/drug therapy , COVID-19/prevention & control , Pandemics/prevention & control , SARS-CoV-2/immunology , Antibodies, Monoclonal/therapeutic use , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Disease Progression , Drug Development , Drug Discovery , Humans , SARS-CoV-2/drug effects , Vaccinology , Viral Vaccines/immunology , Virus Diseases/drug therapy , Virus Diseases/prevention & control
20.
Viruses ; 14(2)2022 02 01.
Article in English | MEDLINE | ID: covidwho-1715768

ABSTRACT

Viral diseases consistently pose a substantial economic and public health burden worldwide [...].


Subject(s)
Antiviral Agents/pharmacology , Virus Diseases/drug therapy , Humans , Virus Diseases/virology , Virus Physiological Phenomena , Viruses/classification , Viruses/drug effects , Viruses/genetics
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