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Antiviral Research Jul 2022In addition to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has become the third... (Review)
Review
In addition to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has become the third deadly coronavirus that infects humans and causes the new coronavirus disease (COVID-19). COVID-19 has already caused more than six million deaths worldwide and it is likely the biggest pandemic of this century faced by mankind. Although many studies on SARS-CoV-2 have been conducted, a detailed understanding of SARS-CoV-2 and COVID-19 is still lacking. Animal models are indispensable for studying its pathogenesis and developing vaccines and antivirals. In this review, we analyze animal models of coronavirus infections and explore their applications on antivirals and vaccines.
Topics: Animals; Antiviral Agents; COVID-19; Middle East Respiratory Syndrome Coronavirus; Models, Animal; SARS-CoV-2; Viral Vaccines; COVID-19 Drug Treatment
PubMed: 35605699
DOI: 10.1016/j.antiviral.2022.105345 -
Discovery Medicine 2021Remdesivir is a broad-spectrum antiviral agent. With the rapid spread of Coronavirus disease 2019 (COVID-19) globally, remdesivir is taking the spotlight for COVID-19...
Remdesivir is a broad-spectrum antiviral agent. With the rapid spread of Coronavirus disease 2019 (COVID-19) globally, remdesivir is taking the spotlight for COVID-19 treatment. Despite the promising signs of anti-CoV activity in several preclinical and clinical studies, more data of remdesivir in the treatment of COVID-19 is still needed for evaluating its efficacy.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34965372
DOI: No ID Found -
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 -
Current Opinion in Immunology Feb 2023The metabolite itaconate (ITA) and its derivatives, both chemically synthesized and endogenous, have emerged as immunoregulators, with roles in limiting inflammation... (Review)
Review
The metabolite itaconate (ITA) and its derivatives, both chemically synthesized and endogenous, have emerged as immunoregulators, with roles in limiting inflammation but also having effects on bacterial and viral infection. Some members of the ITA family have been shown to target and inhibit multiple processes in macrophages with recently identified targets, including NLRP3, JAK1, ten-eleven translocation-2 dioxygenases, and TFEB, a key transcription factor for lysosomal biogenesis. They have also been shown to target multiple bacteria, inhibiting their replication, as well as having antiviral effects against viruses such as SARS-CoV2, Zika virus, and Influenza virus. The importance of ITA is highlighted by the fact that several pathogens have developed mechanisms to evade ITA and can manipulate ITA for their own gain. Two newly discovered isomers of ITA, mesaconate and citraconate, are also discussed, which also have immunomodulatory effects. ITA continues to be a fascination, both in terms of inflammation but also as an antibacterial and antiviral agent, with therapeutic potential in immune and inflammatory diseases.
Topics: Humans; RNA, Viral; COVID-19; SARS-CoV-2; Anti-Infective Agents; Antiviral Agents; Anti-Inflammatory Agents; Inflammation; Zika Virus; Zika Virus Infection
PubMed: 36446152
DOI: 10.1016/j.coi.2022.102268 -
Archives of Microbiology Aug 2018Virus infections are the root cause of epidemics in the world. Vaccines and antiviral agents have been the two important methods to control viral diseases; in recent... (Review)
Review
Virus infections are the root cause of epidemics in the world. Vaccines and antiviral agents have been the two important methods to control viral diseases; in recent times, RNA-mediated therapeutics and prevention have received much attention. In this review, we provide an overview of the current information regarding the use of vaccines, antiviral agents, and RNA-mediated methods in controlling or preventing viral infections. We stress specifically on the potential of existing RNA-mediated methods in clinical applications.
Topics: Animals; Antiviral Agents; Drug Discovery; Humans; RNA, Viral; Virus Diseases; Virus Physiological Phenomena; Viruses
PubMed: 29846759
DOI: 10.1007/s00203-018-1525-z -
European Journal of Medicinal Chemistry Apr 2021In current scenario, various heterocycles have come up exhibiting crucial role in various medicinal agents which are valuable for mankind. Out of diverse range of... (Review)
Review
In current scenario, various heterocycles have come up exhibiting crucial role in various medicinal agents which are valuable for mankind. Out of diverse range of heterocycle, quinoline scaffold have been proved to play an important role in broad range of biological activities. Several drug molecules bearing a quinoline molecule with useful anticancer, antibacterial activities etc have been marketed such as chloroquine, saquinavir etc. Owing to their broad spectrum biological role, various synthetic strategies such as Skraup reaction, Combes reaction etc. has been developed by the researchers all over the world. But still the synthetic methods are associated with various limitations as formation of side products, use of expensive metal catalysts. Thus, several efforts to develop an efficient and cost effective synthetic protocol are still carried out till date. Moreover, quinoline scaffold displays remarkable antiviral activity. Therefore, in this review we have made an attempt to describe recent synthetic protocols developed by various research groups along with giving a complete explanation about the role of quinoline derivatives as antiviral agent. Quinoline derivatives were found potent against various strains of viruses like zika virus, enterovirus, herpes virus, human immunodeficiency virus, ebola virus, hepatitis C virus, SARS virus and MERS virus etc.
Topics: Animals; Antiviral Agents; Cell Line, Tumor; Humans; Quinolines; Virus Diseases; Viruses
PubMed: 33609889
DOI: 10.1016/j.ejmech.2021.113220 -
DICP : the Annals of Pharmacotherapy Jan 1991Cytomegalovirus (CMV), a major opportunistic viral pathogen frequently causing disease in immunocompromised patients such as organ transplant recipients and people with... (Review)
Review
Cytomegalovirus (CMV), a major opportunistic viral pathogen frequently causing disease in immunocompromised patients such as organ transplant recipients and people with AIDS, may present as pneumonitis, gastrointestinal disease, or encephalitis. Its most common manifestation in patients with AIDS is retinitis which, if left untreated, invariably progresses to extensive retinal necrosis and ultimately to blindness. Ganciclovir sodium, currently the only licensed antiviral agent for the treatment of CMV retinitis, effectively controls this infection in a majority of AIDS patients, but significant granulocytopenia or thrombocytopenia related to ganciclovir therapy often limit its clinical application. Myelosuppression may be further exacerbated in AIDS patients by such other agents as zidovudine or trimethoprim/sulfamethoxazole, often necessitating dosage reductions or discontinuation of these agents in patients receiving ganciclovir. Foscarnet sodium, a pyrophosphate analog active against both cytomegalovirus and the human immunodeficiency virus type 1 (HIV), may be an effective alternative to ganciclovir in the management of CMV retinitis. Trials with intravenous foscarnet in CMV retinitis have reported favorable results using initial daily doses of 180-230 mg/kg/d given as intermittent infusions every eight hours, followed by maintenance regimens of 60-90 mg/kg/d given as single daily one- or two-hour infusions. Foscarnet therapy may result in renal impairment, and indefinite intravenous maintenance therapy may be required to prevent recurrence of CMV infection. Despite these drawbacks, foscarnet's lack of major myelosuppressive toxicity, and its activity in suppressing HIV replication, make this a potentially safe and effective alternative agent for the management of CMV infection, especially in AIDS patients.
Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Cytomegalovirus Infections; Eye Infections, Viral; Foscarnet; Herpes Simplex; Humans; Phosphonoacetic Acid; Retinitis
PubMed: 1848959
DOI: 10.1177/106002809102500109 -
International Journal of Toxicology 2022The iminosugar UV-4 is a broad-spectrum antiviral drug candidate with activity and against multiple, diverse viruses. The toxicological profile of UV-4, dosed as the...
The iminosugar UV-4 is a broad-spectrum antiviral drug candidate with activity and against multiple, diverse viruses. The toxicological profile of UV-4, dosed as the hydrochloride salt, was evaluated in single-dose and repeat-dose oral toxicity studies in mice, rats, dogs, and non-human primates (NHP). No moribundity or deaths were associated with the drug up to the maximum tolerated dose. No treatment-related adverse effects were observed following single oral doses in dogs, rats, and mice up to 250, 400, 1000 mg/kg, respectively, and in NHP up to 180 mg/kg administered three times daily for 10 days. UV-4-related findings were generally seen at higher doses after 7- or 14-day exposure. The most common clinical pathology findings (increase in aspartate aminotransferase and decreased platelet count) were consistently found across species and each appeared dose related. The kidney, mesenteric lymph nodes, stomach including gastrointestinal tract, and thymus were identified as target organs in mice, rats, and dogs. In 14-day repeat-dose toxicology studies in mice and dogs conducted in compliance with Good Laboratory Practice regulations, the dog was considered to be the most sensitive species to UV-4 exposure based on the treatment-related adverse effects noted in the identified target organs. The results of these studies demonstrate the safety profile of UV-4 hydrochloride and supported the selection of starting and maximal doses for a single ascending dose first-in-human clinical study.
Topics: Administration, Oral; Animals; Antiviral Agents; Dogs; Drugs, Investigational; Maximum Tolerated Dose; Mice; Rats
PubMed: 35426748
DOI: 10.1177/10915818221077225 -
Antiviral Research Aug 2014Recombinant human interferon-ω (rhIFN-ω) exhibits a potent antiviral activity. Because of poor pharmacokinetics (PK) of rhIFN-ω, frequent dosing of rhIFN-ω is...
Recombinant human interferon-ω (rhIFN-ω) exhibits a potent antiviral activity. Because of poor pharmacokinetics (PK) of rhIFN-ω, frequent dosing of rhIFN-ω is necessitated to achieve the sustained antiviral efficacy. PEGylation can efficiently improve the PK of rhIFN-ω while substantially decrease its bioactivity. The structure, antiviral activity and PK of the PEGylated rhIFN-ω were measured to establish their relationship with PEGylation sites, polyethylene glycol (PEG) mass and PEG structure. Accordingly, N-terminus and the lysine residues were selected as the PEGylation sites. PEGs with Mw of 20kDa and 40kDa were used to investigate the effect of PEG mass. Linear and branched PEGs were used to investigate the effect of PEG structure. PEGylation decreased the antiviral activity of rhIFN-ω and improved its PK. The PEGylation sites determine the bioactivity of the PEGylated rhIFN-ω and the conjugated PEG mass determines the PK. N-terminally PEGylated rhIFN-ω with 40kDa linear PEG maintains 21.7% of the rhIFN-ω antiviral activity with a half-life of 139.6h. Thus, N-terminally PEGylated rhIFN-ω with linear 40kDa PEG is a potential antiviral agent for long-acting treatment of the viral diseases.
Topics: Animals; Antiviral Agents; Interferons; Molecular Weight; Polyethylene Glycols; Rabbits; Structure-Activity Relationship
PubMed: 24936771
DOI: 10.1016/j.antiviral.2014.06.003 -
Current Opinion in Investigational... Nov 2000Pleconaril is an oral antiviral agent being developed by ViroPharma and Sanofi-Synthélabo (formerly Sterling Winthrop) for the potential treatment of several... (Review)
Review
Pleconaril is an oral antiviral agent being developed by ViroPharma and Sanofi-Synthélabo (formerly Sterling Winthrop) for the potential treatment of several picornavirus-induced infections, including respiratory diseases and viral meningitis. A number of phase III clinical trials have been completed, and several others are ongoing [319499], [343187], [346302], [359231]. In early 1999, an NDA filing for viral meningitis was expected by the end of 1999 [313588], [319499]. However, an NDA had not been filed by February 2000 and, at this time, filing in the US was expected in 2000 for viral meningitis and 2001 for viral respiratory syndrome, while in Europe filing was expected in 2001 and 2002 for these indications, respectively [359231]. In July 2000, Salomon Smith Barney predicted a launch date of 2002 [387350]. In October 1999, Lehman Brothers predicted a 70% chance of the product reaching the market, with a possible launch date anticipated for 2001 and potential peak sales of US$50 million in 2009 [346267].
Topics: Antiviral Agents; Clinical Trials as Topic; Contraindications; Drugs, Investigational; Humans; Oxadiazoles; Oxazoles; Picornaviridae; Picornaviridae Infections; Structure-Activity Relationship
PubMed: 11249712
DOI: No ID Found