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Infections
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Fusion inhibitors prevent HIV from entering target cells, by binding to the HIV envelope protein gp41, which is involved in viral entry. By blocking the interactions between regions of the gp41 molecule, fusion inhibitors interfere with the conformational change (folding) of the envelope molecule required for fusion with the target cell membrane.
Infectious Diseases
Published in Kristen Davies, Shadaba Ahmed, Core Conditions for Medical and Surgical Finals, 2020
Nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) target reverse transcriptase. Integrase inhibitors target integrase and protease inhibitors target protease. There are also therapies that aim to prevent the fusion of HIV to immune cells (fusion inhibitors).
Optimising Antiretroviral Therapy Via Pharmacokinetics
Published in Anne George, K. S. Joshy, Mathew Sebastian, Oluwatobi Samuel Oluwafemi, Sabu Thomas, Holistic Approaches to Infectious Diseases, 2017
The fusion inhibitors are of two types:CCR5 co receptor antagonists;Fusion inhibitors.The HIV on entry binds to CCR5 or CXCR4 coreceptor. Maruviroc is for the CCR5-tropic HIV 1 at a dose of 60 mg for 24 weeks shows a good virologic response but hepato toxicity nasopharyngttes, fever presominate (Rieder et al., 2008).The fusion inhibitors enfuvirtide are now being frequently used with local injection reaction, hypersensitivity reaction and pneumonia (Islam et al., 2012).The integrase inhibitors Raltegravir and elvitegravir are commonly used.Potential targets are zinc funger motif inhibitors, HIV glycoprotein membrane domain inhibitors hosT-cell chemokine receptor inhibitors (Gupta et al., 2005).
Therapeutic antibodies and fusion inhibitors targeting the spike protein of SARS-CoV-2
Published in Expert Opinion on Therapeutic Targets, 2021
Shibo Jiang, Xiujuan Zhang, Lanying Du
The S2 protein of human CoVs has been identified as a target to develop broad-spectrum prophylactic and therapeutic antibodies for preventing and treating virus infection. Several SARS-CoV or MERS-CoV S2-specific nAbs have shown neutralizing activity against SARS-CoV or MERS-CoV infection. Different from RBD-specific nAbs, S2-targeting nAbs generally have broad-spectrum neutralizing activity owing to the relatively conserved sequences in S2 region among different CoVs in the same groups. Indeed, some SARS-CoV S2-targeting mAbs do cross-react with SARS-CoV-2 [20]. It appears that no SARS-CoV-2 S2-specific antibodies have been reported so far. Thus, efforts are necessary to develop such mAbs with potent and broad-spectrum neutralizing ability. Except for its role as a neutralizing target, SARS-CoV-2 S2 subunit could also serve as a key target to develop fusion inhibitors to block virus and cell membrane fusion. Such inhibitors have been identified, showing potent inhibitory activity.
Searching for effective antiviral small molecules against influenza A virus: A patent review
Published in Expert Opinion on Therapeutic Patents, 2021
Tiziana Ginex, F. Javier Luque
The fusion inhibitor arbidol was patented in 1993 and is approved for antiviral treatment in Russia [93]. The chemical structure of arbidol and other 5-hydroxy-bromoindole derivatives is shown in Figure 4. Arbidol has a broad-spectrum activity against both influenza A and B with a mean binding affinity (Kd) of 40–100 µM [94], though improvement in binding affinity up to 90–500 nM has been reported for some analogs (general chemical structure 13, with X = O, S; Figure 4) [95] using biolayer interferometry assays to determine the ratio between association and dissociation rate constant of the inhibitor to HA loaded onto streptavidin-coated biosensors (patent published by the Scripps Research Institute in 2018 [96]). The best activity profile was obtained for compound 14, which contains a 2-methylthiophenol moiety, enhancing the binding affinity by 100- and 1000-fold against H1 and H3 strains compared to arbidol.
Envelope proteins as antiviral drug target
Published in Journal of Drug Targeting, 2020
Jyoti Verma, Naidu Subbarao, Maitreyi S. Rajala
Broad spectrum of entry/fusion inhibitors includes natural products such as griffithsin and squalamine inhibiting number of viruses, including flaviviruses. Another such compound is an indole-derivative arbidol, which inhibits membrane fusion by impending the conformational changes of fusion peptide during virus fusion [59,60]. A selective inhibitor, GS-563253 (HCV II-1) of HCV genotypes 1 and 2 was reported with low nanomolar EC50 preventing the endosomal fusion [61]. A group of researchers established a competitive amplified luminescent proximity homogeneous assay (ALPHAscreen) through which they identified small molecule inhibitors targeting envelope protein mediated membrane fusion of Zika virus [62]. They also report seven lead compounds having potent activity against the closely related dengue virus 2 but not vesicular stomatitis virus G protein which is a class III fusion protein. Chloroquine has been reported to block the expression of VSV glycoprotein G and addition of 50 mg/ml of chloroquine prevented virus induced cell fusion [63]. Since, chloroquine prevents endosomal acidification; it blocks the fusion of the virus with the endosomal membrane. Hence, chloroquine and its analogs have potential for the treatment of endosomal low pH dependent emerging viruses. Small molecule inhibitors with strong fusion inhibitor activity either with plasma membrane or with the endosomal membrane can be successful antiviral drugs.