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World Journal of Gastroenterology Apr 2023The tremendous public health and economic impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has... (Review)
Review
The tremendous public health and economic impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type III interferon (IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARS-CoV-2, including its invasion and immune escape mechanisms. Emphasis was placed on the gastrointestinal impact of SARS-CoV-2, including changes to the intestinal microbiome, activation of immune cells, and inflammatory responses. We also describe the comprehensive functions of IFN-λ in anti-enteric SARS-CoV-2 infection, and discuss the potential application of IFN-λ as a therapeutic agent for COVID-19 with intestinal symptoms.
Topics: Humans; COVID-19; Interferon Lambda; SARS-CoV-2; Interferons; Antiviral Agents
PubMed: 37155525
DOI: 10.3748/wjg.v29.i13.1942 -
Naunyn-Schmiedeberg's Archives of... Oct 2023Viral diseases are the most notorious infective agent(s) causing morbidity and mortality in every nook and corner for ages; viruses are active in host cells, and... (Review)
Review
Viral diseases are the most notorious infective agent(s) causing morbidity and mortality in every nook and corner for ages; viruses are active in host cells, and specific anti-virus medicines' developments remain uncanny. In this century of the biological era, human viruses act predominantly as versatile spreaders. The infection of the present COVID-19 virus is up in the air; blithely, the integument of medicinal chemistry approaches, particularly bioactive derived phytocompounds could be helpful to control those human viruses, recognized in the last 100 years. Indeed, natural products are being used for various therapeutic purposes. The major bioactive phytocompounds are chemically containing coumarin, thiosulfonate, steroid, polysaccharide, tannin, lignin, proanthocyanidin, terpene, quinone, saponin, flavonoid, alkaloid, and polyphenol, that are documented for inhibitory action against several viral infections. Mostly, about 20-30% of plants from tropical or temperate regions are known to have some antiviral activity. This comprehensive analysis of bioactive-derived phytocompounds would represent a significant impact and might be helpful for antiviral research and the current state of viral treatments.
Topics: Humans; Antiviral Agents; COVID-19; SARS-CoV-2
PubMed: 37160482
DOI: 10.1007/s00210-023-02517-2 -
Scientific Reports Feb 2023Remdesivir (GS-5734; VEKLURY) is a single diastereomer monophosphoramidate prodrug of an adenosine analog (GS-441524). Remdesivir is taken up by target cells and...
Remdesivir (GS-5734; VEKLURY) is a single diastereomer monophosphoramidate prodrug of an adenosine analog (GS-441524). Remdesivir is taken up by target cells and metabolized in multiple steps to form the active nucleoside triphosphate (GS-443902), which acts as a potent inhibitor of viral RNA-dependent RNA polymerases. Remdesivir and GS-441524 have antiviral activity against multiple RNA viruses. Here, we expand the evaluation of remdesivir's antiviral activity to members of the families Flaviviridae, Picornaviridae, Filoviridae, Orthomyxoviridae, and Hepadnaviridae. Using cell-based assays, we show that remdesivir can inhibit infection of flaviviruses (such as dengue 1-4, West Nile, yellow fever, Zika viruses), picornaviruses (such as enterovirus and rhinovirus), and filoviruses (such as various Ebola, Marburg, and Sudan virus isolates, including novel geographic isolates), but is ineffective or is significantly less effective against orthomyxoviruses (influenza A and B viruses), or hepadnaviruses B, D, and E. In addition, remdesivir shows no antagonistic effect when combined with favipiravir, another broadly acting antiviral nucleoside analog, and has minimal interaction with a panel of concomitant medications. Our data further support remdesivir as a broad-spectrum antiviral agent that has the potential to address multiple unmet medical needs, including those related to antiviral pandemic preparedness.
Topics: Humans; Antiviral Agents; Adenosine Monophosphate; Alanine; Hemorrhagic Fever, Ebola; Filoviridae; Zika Virus; Zika Virus Infection
PubMed: 36823196
DOI: 10.1038/s41598-023-29517-9 -
Molecules (Basel, Switzerland) May 2023Compounds with acylhydrazone fragments contain amide and imine groups that can act as electron donors and acceptors, so they are easier to bind to biological targets and...
Compounds with acylhydrazone fragments contain amide and imine groups that can act as electron donors and acceptors, so they are easier to bind to biological targets and thus generally exhibit significant biological activity. In this work, acylhydrazone fragments were introduced to the C-14 or C-11 position of matrine, a natural alkaloid, aiming to enhance their biological activities. The result of this bioassay showed that many synthesized compounds exhibited excellent anti-virus activity against the tobacco mosaic virus (TMV). Seventeen out of 25 14-acylhydrazone matrine derivatives and 17 out of 20 11-butanehydrazone matrine derivatives had a higher inhibitory activity against TMV than the commercial antiviral agent Ribavirin (the in vitro activity, in vivo inactivation, curative and protection activities at 500 µg/mL were 40.9, 36.5 ± 0.9, 38.0 ± 1.6 and 35.1 ± 2.2%, respectively), and four 11-butanehydrazone matrine derivatives even had similar to or higher activity than the most efficient antiviral agent Ningnanmycin (55.4, 57.8 ± 1.4, 55.3 ± 0.5 and 60.3 ± 1.2% at 500 µg/mL for the above four test modes). Among them, the -benzyl-11-butanehydrazone of matrine formed with 4-bromoindole-3-carboxaldehyde exhibited the best anti-TMV activity (65.8, 71.8 ± 2.8, 66.8 ± 1.3 and 69.5 ± 3.1% at 500 µg/mL; 29, 33.5 ± 0.7, 24.1 ± 0.2 and 30.3 ± 0.6% at 100 µg/mL for the above four test modes), deserving further investigation as an antiviral agent. Other than these, the two series of acylhydrazone-containing matrine derivatives were evaluated for their insecticidal and fungicidal activities. Several compounds were found to have good insecticidal activities against diamondback moth () and mosquito larvae (), showing broad biological activities.
Topics: Animals; Molecular Structure; Structure-Activity Relationship; Matrines; Insecticides; Tobacco Mosaic Virus; Moths; Antiviral Agents; Drug Design
PubMed: 37241904
DOI: 10.3390/molecules28104163 -
Nucleoside analogs as a rich source of antiviral agents active against arthropod-borne flaviviruses.Antiviral Chemistry & Chemotherapy 2018Nucleoside analogs represent the largest class of small molecule-based antivirals, which currently form the backbone of chemotherapy of chronic infections caused by HIV,... (Review)
Review
Nucleoside analogs represent the largest class of small molecule-based antivirals, which currently form the backbone of chemotherapy of chronic infections caused by HIV, hepatitis B or C viruses, and herpes viruses. High antiviral potency and favorable pharmacokinetics parameters make some nucleoside analogs suitable also for the treatment of acute infections caused by other medically important RNA and DNA viruses. This review summarizes available information on antiviral research of nucleoside analogs against arthropod-borne members of the genus Flavivirus within the family Flaviviridae, being primarily focused on description of nucleoside inhibitors of flaviviral RNA-dependent RNA polymerase, methyltransferase, and helicase/NTPase. Inhibitors of intracellular nucleoside synthesis and newly discovered nucleoside derivatives with high antiflavivirus potency, whose modes of action are currently not completely understood, have drawn attention. Moreover, this review highlights important challenges and complications in nucleoside analog development and suggests possible strategies to overcome these limitations.
Topics: Animals; Antiviral Agents; Culicidae; Flavivirus; Flavivirus Infections; Microbial Sensitivity Tests; Molecular Structure; Nucleosides
PubMed: 29534608
DOI: 10.1177/2040206618761299 -
European Journal of Medicinal Chemistry Oct 2023The major severe complications linked to Zika virus (ZIKV) cause the global public health problems, including microcephaly and other congenital abnormalities in...
The major severe complications linked to Zika virus (ZIKV) cause the global public health problems, including microcephaly and other congenital abnormalities in newborns, and Guillain-Barré syndrome, meningoencephalitis, multi-organ failure in adults. However, neither approved vaccines nor drugs are available for ZIKV. In this study, we describe the design, synthesis and the anti-ZIKV activities of a series of anthraquinone analogs. Most of the newly synthesized compounds demonstrated moderate to excellent potency against ZIKV. Among all, compound 22, showed the most potent anti-ZIKV activity (EC value from 1.33 μM to 5.72 μM) with low cytotoxicity (CC>50 μM) in multiple cellular model. Importantly, 22 significantly improved the survival of ZIKV-infected mice (Ifnar1), alleviated ZIKV-associated pathological damages and suppressed the excessive inflammatory response and pyroptosis induced by ZIKV in vivo and in vitro. Furthermore, the molecular docking simulation analysis and the surface plasmon resonance results demonstrated the direct binding between 22 and ZIKV RdRp, and the mechanistic study revealed that 22 suppressed viral RNA synthesis by ZIKV NS5 in cells. Taken together, this study highlights that 22 may be a novel anti-ZIKV drug candidate and provides treatment options for ZIKV-associated diseases.
Topics: Animals; Mice; Zika Virus; Antiviral Agents; Molecular Docking Simulation; Virus Replication; Zika Virus Infection
PubMed: 37421888
DOI: 10.1016/j.ejmech.2023.115620 -
Molecules (Basel, Switzerland) Apr 2022Since COVID-19 has affected global public health, there has been an urgency to find a solution to limit both the number of infections, and the aggressiveness of the... (Review)
Review
Since COVID-19 has affected global public health, there has been an urgency to find a solution to limit both the number of infections, and the aggressiveness of the disease once infected. The main characteristic of this infection is represented by a strong alteration of the immune system which, day by day, increases the risk of mortality, and can lead to a multiorgan dysfunction. Because nutritional profile can influence patient's immunity, we focus our interest on resveratrol, a polyphenolic compound known for its immunomodulating and anti-inflammatory properties. We reviewed all the information concerning the different roles of resveratrol in COVID-19 pathophysiology using PubMed and Scopus as the main databases. Interestingly, we find out that resveratrol may exert its role through different mechanisms. In fact, it has antiviral activity inhibiting virus entrance in cells and viral replication. Resveratrol also improves autophagy and decreases pro-inflammatory agents expression acting as an anti-inflammatory agent. It regulates immune cell response and pro-inflammatory cytokines and prevents the onset of thrombotic events that usually occur in COVID-19 patients. Since resveratrol acts through different mechanisms, the effect could be enhanced, making a totally natural agent particularly effective as an adjuvant in anti COVID-19 therapy.
Topics: Anti-Inflammatory Agents; Antiviral Agents; Dietary Supplements; Humans; Resveratrol; COVID-19 Drug Treatment
PubMed: 35458574
DOI: 10.3390/molecules27082376 -
Molecules (Basel, Switzerland) Mar 2017This review illustrates the various studies made to investigate the activity of -pyrrylarylsulfone containing compounds as potential antiviral, anticancer and SNC drugs.... (Review)
Review
This review illustrates the various studies made to investigate the activity of -pyrrylarylsulfone containing compounds as potential antiviral, anticancer and SNC drugs. A number of synthetic approaches to obtain tetracyclic, tricyclic and non-cyclic compounds, and their biological activity with regard to structure-activity relationships (SARs) have been reviewed. The literature reviewed here may provide useful information on the potential of -pyrrylarylsulfone pharmacophore as well as suggest concepts for the design and synthesis of new -pyrrylarylsulfone based agents.
Topics: Antineoplastic Agents; Antiviral Agents; Chemistry Techniques, Synthetic; Humans; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Sulfonamides
PubMed: 28282943
DOI: 10.3390/molecules22030434 -
European Journal of Medicinal Chemistry Oct 2020The new virus of the of β-Coronaviruses genus, SARS-CoV-2, is the causative agent of coronavirus disease-2019 (COVID-19) and is winning a proverbial chess match against... (Review)
Review
The new virus of the of β-Coronaviruses genus, SARS-CoV-2, is the causative agent of coronavirus disease-2019 (COVID-19) and is winning a proverbial chess match against all players simultaneous, including physicians, clinicians, pathologists, doctors, scientists, economists, athletes and politicians. The COVID-19 outbreak has seriously threatened public health, killing the most vulnerable persons and causing general panic. To stop this disease, effective remedies (i.e., drugs, vaccines, personal protection elements, etc.) are urgently required. Unfortunately, no registered specific therapies (including antiviral therapies, immune-modulating agents and vaccines) are currently available to treat coronavirus infections, highlighting an urgent need for therapeutics targeting SARS-CoV-2. In this work, fourteen existing small molecule drugs or/and experimental drugs selected by experts and examined from the point of view of bioavailability via the Lipinski-Veber rules and assessment of their physicochemical descriptors. The aim of this study is to discover selected pattern similarities and peculiar characteristics that could be useful for antiviral drug optimization, drug combination or new antiviral agent design.
Topics: Animals; Antiviral Agents; Betacoronavirus; Biological Availability; COVID-19; COVID-19 Vaccines; Coronavirus Infections; Drug Combinations; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Viral Vaccines; COVID-19 Drug Treatment
PubMed: 32693298
DOI: 10.1016/j.ejmech.2020.112647 -
Microbiology Spectrum Feb 2023The periodic emergence of infectious disease poses a serious threat to human life. Among the causative agents, including pathogenic bacteria and fungi, enveloped viruses...
The periodic emergence of infectious disease poses a serious threat to human life. Among the causative agents, including pathogenic bacteria and fungi, enveloped viruses have caused global pandemics. In the last 10 years, outbreaks of severe acute respiratory syndrome coronavirus 2 disease, severe acute respiratory syndrome, and Middle East respiratory syndrome have all been caused by enveloped viruses. Among several paths of secondary transmission, inhalation of aerosols containing saliva with sputum droplets from infected patients is the major path. To prevent these infectious diseases, mass use of antiviral agents is essential. The yeast-derived vacuole is a small organelle in which hydrolytic enzymes are concentrated. It is an intracellular organ with an excellent ability to process old organelles and bacteria and viruses that have invaded from the outside and can be present in sufficient quantity to be called a kind of enzyme bomb. We confirmed the inhibition of virus infection and structural collapse by vacuole treatment. Among several enzymes, proteases affected Phi6 infectivity. This study tried to isolate these vacuoles from yeast and use them as an antiviral agent for virus treatment, which is a recent issue. We confirmed that viral infectivity was inactivated, and structure collapsed through vacuole treatment. This paper is meaningful in that extracellularly isolated yeast-derived vacuoles are a first attempt to utilize vacuoles for viral treatment. The study assesses the vacuoles isolated from the yeast Saccharomyces cerevisiae as green antiviral agents to decrease the concerns about massive use of chemical antiviral agents and its side effects. To prevent the spreading of infectious diseases, personal or public use of antiviral agents is encouraged. The concern about the active compounds of these chemical antiviral agents has grown. Active compounds of antiviral agents have potential side effects on human health and the environment. Our proposed approach suggests effective and green antivirus material from a nonhazardous yeast strain. Also, large-scale production using a fermentation process can allow cost-effectiveness. The results showed sufficient reduced infectivity by vacuole treatment. The exposed vacuole can play the roles of both enzyme bomb to the virus and renewable nutrient source in the ecosystem.
Topics: Humans; Saccharomyces cerevisiae; Vacuoles; Ecosystem; COVID-19; Viruses; Antiviral Agents
PubMed: 36688634
DOI: 10.1128/spectrum.02661-22