The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform

Keivan Zandi - One of the best experts on this subject based on the ideXlab platform.

  • baicalein and baicalin as zika virus inhibitors
    Archives of Virology, 2019
    Co-Authors: Boonteong Teoh, Keivan Zandi, Singsin Sam, Sazaly Abu Bakar
    Abstract:

    At present, there is no effective Antiviral Agent for Zika virus (ZIKV), an arbovirus that is known for its teratogenic effects on newborns. Baicalein and baicalin were found to be capable of downregulating ZIKV replication up to 10 hours postinfection, while prophylactic effects were evident in pre-treated cells. Baicalein exhibited its highest potency during intracellular ZIKV replication, whereas baicalin was most effective against virus entry. Our in silico interaction assays predicted that both compounds exhibited the strongest binding affinities towards ZIKV NS5, while the virus envelope glycoprotein was the least likely target protein. These findings serve as a crucial platform for further in-depth studies to decipher the underlying anti-ZIKV mechanism(s) of each compound.

  • deciphering the potential of baicalin as an Antiviral Agent for chikungunya virus infection
    Antiviral Research, 2018
    Co-Authors: Kai Rausalu, Keivan Zandi, Sazaly Abu Bakar, Andres Merits, Stephen Higgs, Dana L Vanlandingham
    Abstract:

    Abstract The past decade has seen the re-emergence of Chikungunya virus (CHIKV) as a major global health threat, affecting millions around the world. Although fatal infections are rare among infected patients, the occurrence of long-lasting polyarthralgia has a significant impact on patients' quality of lives and ability to work. These issues were the stimuli for this study to determine the potential of baicalin, a bioflavonoid, as the novel Antiviral compound against CHIKV. It was found that baicalin was well tolerated by Vero, BHK-21 and HEK 293T cells with maximal nontoxic doses >600 μM, ≈ 350 μM and ≈110 μM, respectively. Antiviral assays indicated that baicalin was the most effective inhibitor when tested for its direct virucidal activity with EC 50  ≈ 7 μM, followed by inhibition of virus entry into the host cell, attachment of virus particle to cellular receptors and finally intracellular replication of viral RNA genome. In silico analysis using molecular docking demonstrated close interactions between baicalin and CHIKV envelope protein with considerably strong binding affinity of −9.7 kcal/mol. qRT-PCR analysis revealed that baicalin had the greatest effect on the synthesis of viral negative stand RNA with EC 50  ≈ 0.4 μM followed by the inhibition of synthesis of positive-strand genomic (EC 50  ≈ 13 μM) and subgenomic RNAs (EC 50  ≈ 14 μM). These readings indicate that the compound efficiently inhibits replicase complexes formation but is a less potent inhibitor of existing replicase complexes. Coherent with this hypothesis, the use of recombinant CHIKV replicons harboring Renilla luciferase marker showed that replication of corresponding replicon RNAs was only slightly downregulated at higher doses of baicalin, with EC 50  > 100 μM. Immunofluorescence and western blotting experiments demonstrated dose-dependent inhibition of expression of different viral proteins. It was also observed that levels of important protein markers for cellular autophagy (LC3) and apoptosis (Bax) were reduced in baicalin treatment groups as compared with untreated virus infected controls. In summary, given its low toxicity and high efficacy against CHIKV, baicalin has great potential to be developed as the novel Antiviral compound for CHIKV. In vivo studies to evaluate its activity in a more complexed system represent a necessary step for future analysis.

  • in silico study on baicalein and baicalin as inhibitors of dengue virus replication
    RSC Advances, 2016
    Co-Authors: Pouya Hassandarvish, Hussin A Rothan, Sahar Rezaei, Rohana Yusof, Sazaly Abubakar, Keivan Zandi
    Abstract:

    The dengue virus (DENV) is an important human arbovirus that belongs to the Flaviviridae. Currently, there is no vaccine or effective Antiviral Agent against DENV. Therefore, finding an efficient Antiviral Agent against this virus is crucial. We have previously reported the anti-DENV activity of two flavonoids, namely, baicalein and baicalin, against different stages of the virus replication cycle in Vero cells. In this study, we aimed to predict the possible interactions between viral proteins that are important for DENV replication and these two flavonoids as potential candidates for anti-DENV drug discovery with known in vitro anti-DENV activity. In this study, the interactions between compounds of interest and three important proteins of DENV were predicted using appropriate software. Moreover, the binding energy between these compounds and selected proteins was calculated as one of the main criteria for molecular docking studies. The results showed that both compounds of interest, as ligands, can bind with chosen viral proteins, as receptors, through hydrogen bonding and other interactions such as pi–pi interactions, pi–sigma interactions and pi–cation interactions. The obtained data showed significant affinity between the tested compounds and the NS2B–NS3 protease of DENV. Therefore, an in vitro anti-protease assay was conducted and the results showed significant anti-DENV protease activity for both compounds, especially baicalein. In conclusion, our obtained data showed that both tested compounds can affect DENV intracellular replication and internalization. However, these results support our previous findings from in vitro studies and encourage us to further studies towards finding the mechanism of action of these compounds.

Xi Zhou - One of the best experts on this subject based on the ideXlab platform.

  • cucurbit 7 uril as a broad spectrum Antiviral Agent against diverse rna viruses
    Virologica Sinica, 2021
    Co-Authors: Jia Quan, Xiangjun Zhang, Yuanfu Ding, Yang Qiu, Ruibing Wang, Xi Zhou
    Abstract:

    The emergence and re-emergence of RNA virus outbreaks highlight the urgent need for the development of broad-spectrum Antivirals. Polyamines are positively-charged small molecules required for the infectivity of a wide range of RNA viruses, therefore may become good Antiviral targets. Cucurbit[7]uril (CB[7]), a synthetic macrocyclic molecule, which can bind with amine-based organic compounds with high affinity, has been shown to regulate bioactive molecules through competitive binding. In this study, we tested the Antiviral activity of CB[7] against diverse RNA viruses, including a panel of enteroviruses (i.e. human enterovirus A71, coxsackievirus A16, coxsackievirus B3, and echovirus 11), some flaviviruses (i.e. dengue virus and Zika virus), and an alphavirus representative Semliki forest virus. CB[7] can inhibit virus replications in a variety of cell lines, and its mechanism of action is through the competitive binding with polyamines. Our findings not only for the first time provide evidence that CB[7] can be a promising broad-spectrum Antiviral Agent, but more importantly, offer a novel therapeutic strategy to fight against RNA viruses by supramolecular sequestration of polyamines.

Rafael Esteban - One of the best experts on this subject based on the ideXlab platform.

  • management of direct Antiviral Agent failures
    Clinical and molecular hepatology, 2016
    Co-Authors: Maria Buti, Rafael Esteban
    Abstract:

    The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting Antiviral Agents (DAAs). Most HCV patients treated with these drugs achieve viral elimination, but 1% to 15% fail to attain this objective. Treatment failures are usually related to relapse, and less often to on-treatment viral breakthrough. HCV drug resistant associated substitutions are detected in most patients who do not eliminate the virus. The risk of developing these variants depends on host- and virus-related factors, the properties of the drugs used, and the treatment strategies applied. Patients who carry Resistant Associated Substitutions (RASs) may not obtain benefits from treatment, and are at a risk of disease progression. Whether HCV RASs persist depends on their type: NS3-4A variants often disappear gradually after DAA therapy is stopped, whereas NS5A variants tend to persist for more than 2 years. The best way to prevent emergence of resistant variants is to eliminate the virus at the first treatment using highly potent DAAs with genetic barriers to resistance. For those who fail an NS5A inhibitor, deferral of treatment is recommended pending the availability of additional data if they do not have cirrhosis or reasons for urgent re-treatment. If re-treatment is needed, the most commonly used strategy is sofosbuvir as backbone therapy plus a drug from a class other than that previously used, for 24 weeks. Unless it is contraindicated, weight-based ribavirin should also be added. If available, nucleotide-based (eg, sofosbuvir) triple or quadruple DAA regimens may be considered. The optimal treatment for patients who fail an NS5A inhibitor and those with multidrug-resistant variants remains to be defined, and research efforts should continue to focus on treatment for these patients.

  • management of direct acting Antiviral Agent failures
    Journal of Hepatology, 2015
    Co-Authors: Maria Buti, Rafael Esteban, Mar Riveirobarciela
    Abstract:

    Failure to respond to the approved combinations of multiple direct-acting Antiviral Agents is relatively low in hepatitis C virus treatment registration studies, with rates of 1% to 7%, depending on the patients' baseline characteristics. In real life, failure is slightly higher, likely because of lower compliance. Treatment failures are usually related to relapse and less often to on-treatment viral breakthrough. Hepatitis C drug-resistant variants are detected in most patients who do not achieve viral eradication. The risk of developing these variants depends on host- and virus-related factors, the properties of the drugs used, and the treatment strategies applied. Patients who carry resistance-associated variants may not obtain benefits from treatment and are at risk of disease progression and transmission of the variants. Whether hepatitis C resistance-associated variants persist depends on their type: NS3-4A variants often disappear gradually after therapy is stopped, whereas NS5A variants tend to persist for more than 2 years. The best way to prevent emergence of resistant variants is to eliminate the virus at the first treatment using highly potent Antivirals with genetic barriers to resistance. In patients failing first-generation protease inhibitors, combination therapies with sofosbuvir and NS5 inhibitors have proven effective. Some salvage regimens can be shortened to 12 weeks by addition of ribavirin. The optimal treatment for patients who fail an NS5A inhibitor and those with multidrug-resistant variants remains to be defined, and research efforts should continue to focus on treatment for these patients.

Jia Zhou - One of the best experts on this subject based on the ideXlab platform.

  • broad spectrum Antiviral Agent niclosamide and its therapeutic potential
    ACS Infectious Diseases, 2020
    Co-Authors: Pei Yong Shi, Jia Zhou
    Abstract:

    The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide, an FDA-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as SARS-CoV, MERS-CoV, ZIKV, HCV, and human adenovirus, indicating its potential as an Antiviral Agent. In this brief review, we summarize the broad Antiviral activity of niclosamide and highlight its potential clinical use in the treatment of COVID-19.

John M. Taylor - One of the best experts on this subject based on the ideXlab platform.

  • squalamine as a broad spectrum systemic Antiviral Agent with therapeutic potential
    Proceedings of the National Academy of Sciences of the United States of America, 2011
    Co-Authors: Michael Zasloff, Bernard Beckerman, Ann E Campbell, Erik Luijten, Isaura Meza, Justin G Julander, Wei Qu, Paige A Adams, Abhijit Mishra, John M. Taylor
    Abstract:

    Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum Antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacity of squalamine, a cationic amphipathic sterol, to neutralize the negative electrostatic surface charge of intracellular membranes in a way that renders the cell less effective in supporting viral replication. Because squalamine can be readily synthesized and has a known safety profile in man, we believe its potential as a broad-spectrum human Antiviral Agent should be explored.