China
Africa
Explore chapters and articles related to this topic
Current Inhibitors of Dengue Virus
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
J. Jonathan Harburn, G. Stuart Cockerill
Viral entry inhibition is historically a logical approach to virus inhibition. Inhibitors act early in the life cycle of the virus and therefore find a role in treating infection early and subsequent re-infection as the virus life cycle continues. Initial entry inhibitors identified were based upon peptide sequences derived from the structure of the envelope E protein, a protein core to the fusion process of the virus with target cell and a protein that undergoes a significant conformational effect during the fusion process. Analogies with other virus fusion events are not unreasonable (Battles et al. 2016). Initial peptides screened were large, with 33 residues, and not potent (Hrobowski et al. 2005). Truncated and mutated forms of these peptides were identified, although still of significant size (Schmidt and Harrison 2010). A series of smaller tripeptides were found to be of low activity (Panya et al. 2014).
Chemokine Receptors as HIV-1 Coreceptors
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
The recent observation that simultaneous inhibition of HIV-1 reverse transcriptase and protease does not prevent viral resistance, and will not be sufficient for viral eradication (67), underscores the pressing need for new classes of antiviral drugs. One plausible target for such agents is HIV-1 entry into CD4+ cells, as shown by clinical trials of the fusion inhibitor T20, a peptide that prevents the functioning of the viral gp41 protein (68). Other targets for entry inhibitors include the major cell surface entry coreceptors CCR5 and CXCR4 that, with CD4, mediate virus binding and membrane fusion (69). As CCR5, but not CXCR4, is apparently dispensable for normal health (69), specific inhibition of CCR5 function is an attractive concept. It is, however, one not without potential pitfalls. Concern exists on whether CCR5 inhibitors might select for new, and possibly more pathogenic, viral variants which instead use CXCR4 (“virologic toxicity”).
Blood-Borne Viruses in Clinical and Diagnostic Virology
Published in Attila Lorincz, Nucleic Acid Testing for Human Disease, 2016
Hubert G.M. Niesters, Martin Schutten, Elisabeth Puchhammer-Stöckl
Viral entry inhibitors represent the latest class of antiretroviral drugs. The two distinct types of entry inhibitors are (1) those inhibiting the fusion process (with T20 from Hoffmann-La Roche Ltd, Basel, Switzerland, the only current representative) and (2) those that inhibit binding to the second receptor. Of the latter group, several drugs that inhibit CXCR-4 and CCR-5, the two major second receptors used by HIV, are currently in Phase III clinical trials. It does not seem logical to assume that entry inhibitors will ever be used in first-line therapy since second receptor inhibitors inhibit either CXCR-4 or CCR-5 and up-front screening of second receptor usage for first-line regimens does not seem likely at present. T20 has the disadvantage that it cannot be administered orally. Recently an antiretroviral drug was described as belonging to a new class of nucleotide-competing reverse transcriptase inhibitors. Whether this drug will successfully complete clinical trials and achieve market distribution is unknown.
Effects of statins on the risks of ischemic stroke and heart disease in human immunodeficiency virus infection, influenza and severe acute respiratory syndrome–associated coronavirus: respiratory virus infection with steroid use
Published in Postgraduate Medicine, 2022
Jun-Jun Yeh, Meichu Lai, Cheng-Li Lin, Kuan-Hua Lu, Chia-Hung Kao
Attenuating the viral load in HIS disorders may play an auxiliary role in lowering the risk of ischemic stroke and heart disease. Because they are entry inhibitors, antiviral biomaterials may be able to bind to viruses. These biomaterials could interfere with replication of viral nucleic acid, such as ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and induce irreversible viral deformation [45–47]. Therefore, antiviral biomaterial may play a critical role in modulating risks in HIS disorders. Reports indicate that reconstituted high-density lipoprotein (rHDL) may be a synthetic form of endogenous plasma HDL. Furthermore, monosialotetrahexosylganglioside (GM1) modification of statin-loaded rHDL could induce enhanced inhibition of atherogenesis, atherosclerosis, and related disease activity. This finding indicates that statin–GM1–rHDL may be employed as a drug delivery system to treat ischemic stroke and heart disease [48,49].
Evaluating fostemsavir as a therapeutic option for patients with HIV
Published in Expert Opinion on Pharmacotherapy, 2021
Marco Berruti, Rachele Pincino, Lucia Taramasso, Antonio Di Biagio
Entry inhibitors are second-line agents that prevent HIV-1 cellular entry through binding a viral cellular target. Enfuvirtide and maraviroc were the first drugs to use this mechanism of action, as they targeted, respectively, the cellular glycoprotein 41 and the CCR5 receptor. However, these drugs have both been shown to have a lower virologic efficacy or little advantage [13–17] with respect to comparators in more recent years. In addition, the disadvantageous method of administering enfuvirtide, namely subcutaneous administration twice daily while maintaining the cold chain, hampered the diffusion of its use out of the context of strict clinical need. For maraviroc, besides the low efficacy in the naïve and experienced PWH [15,18,19], there was the additional need for tropism testing before prescription, which limited its use. Recently two new drug members of this class are entering the market: ibalizumab and fostemsavir.
Fostemsavir for the treatment of HIV
Published in Expert Review of Anti-infective Therapy, 2021
Nikhil Seval, Cynthia Frank, Michael Kozal
The entry inhibitors are a broad categorization of antiretroviral agents that are often used in drug regimens when the first-line drug classes are limited. Maraviroc, a CCR5 chemokine receptor antagonist, is limited in its indication to those with R5 tropic virus and can be complicated by both hepatotoxicity and drug–drug interactions. Enfuvirtide binds to the gp41 subunit of the HIV viral envelope protein thus preventing fusion and entry into CD4 cells – it is subcutaneous injection whose a twice-a-day administration is often found to be too cumbersome by patients. Ibalizumab is a recombinant monoclonal antibody that was FDA approved in 2018 and functions as a ‘post-attachment’ inhibitor by binding to domain 2 of CD4 cells. It requires an infusion every 2 weeks that may not be feasible for all patients. Fostemsavir represents the addition of a new drug class to the market in an oral formulation with a favorable tolerability profile.