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- W3136354265 abstract "ABSTRACTIntroduction: SARS-CoV-2 has fatally affected the whole world with millions of deaths. Amidst the dilemma of a breakthrough in vaccine development, hydroxychloroquine (HCQ) was looked upon as a prospective repurposed candidate. It has confronted numerous controversies in the past few months as a chemoprophylactic and treatment option for COVID-19. Recently, it has been withdrawn by the World Health Organization for its use in an ongoing pandemic. However, its benefit/risk ratio regarding its use in COVID-19 disease remains poorly justified. An extensive literature search was done using Scopus, PubMed, Google Scholar, www.cdc.gov, www.fda.gov, and who.int.Areas covered: Toxicity vexations of HCQ; pharmaceutical perspectives on new advances in drug delivery approaches; computational modeling (PBPK and PD modeling) overtures; multipronged combination approaches for enhanced synergism with antiviral and anti-inflammatory agents; immuno-boosting effects.Expert commentary: Harnessing the multipronged pharmaceutical perspectives will optimistically help the researchers, scientists, biotech, and pharmaceutical companies to bring new horizons in the safe and efficacious utilization of HCQ alone or in combination with remdesivir and immunomodulatory molecules like bovine lactoferrin in a fight against COVID-19. Combinational therapies with free forms or nanomedicine based targeted approaches can act synergistically to boost host immunity and stop SARS-CoV-2 replication and invasion to impede the infection.KEYWORDS: SARS-CoV-2toxicityhydroxychloroquinepharmaceutical considerationsdrug deliveryimmunomodulationcombinational therapyremdesivirangiotensin-converting enzyme-2 Article HighlightsSafe and effective use of hydroxychloroquine (HCQ) in a battle with COVID-19 for chemoprophylaxis and treatment.Various HCQ associated toxicities with considerable benefit/risk ratio for vulnerable population.Pharmaceutical advances based on computational modelling (PBPK and PD modelling) with recent advances in drug delivery approaches.Retrospective learnings for dose adjustment for the vulnerable population.Multipronged combination approaches for enhanced synergism with antiviral and anti-inflammatory agents, and immuno-boosting effects.Declaration of interestA. Jain gratefully acknowledges financial support from the DBT-RA program (Govt. of India) in Biotechnology and Life Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.AbbreviationsAbs AntibodiesACE Angiotensin Convertase EnzymeACEIs ACE inhibitorAKI Acute kidney injuryARDS Acute respiratory distress syndromeAZT AzithromycinB.I.D. Two times a dayBDCQ BisdesethylchloroquinebLf Bovine lactoferrinCADD Computer-aided drug designCDC Centres for Disease Control and PreventioncGAS GMP-AMP SynthaseCOPD Chronic Obstructive Pulmonary DiseaseCQ ChloroquineDCGI Drug Controller General of IndiaDCQ DesethylchloroquineDHCQ DesethylhydroxychloroquineDMT1 Divalent metal transporter 1EC50Half maximal effective concentrationG6PD Glucose-6-Phosphate DehydrogenasGI GastrointestinalHCoVs Human coronavirusesHCQ HydroxychloroquineHSPGs Heparan sulfate proteoglycanesIC50Half maximal inhibitory concentrationICMR Indian Council of Medical Research)IL InterleukinMAP Mitogen-Activated ProteinMHC Major Histocompatibility ComplexMpro Main proteaseNAC N- acetyl-cysteineNIMHANS National School of Mental Health and NeurosciencesNYR Not yet recruitingPBPK Pharmacokinetic modelsPBPK Physiologically based pharmacokineticPD PharmacodynamicPGA-co-PDL Poly(glycerol adipate-co-ω-pentadecalactone)PICALM Phosphatidylinositol Binding Clathrin Assembly ProteinQ.D. Once in a dayQIVIVE Quantitative in vitro to in vivo extrapolationRPE Retinal pigment epitheliumSTING Stimulator of Interferon GenesT.I.D. Three times a dayTB Tuberculosis" @default.
- W3136354265 created "2021-03-29" @default.
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- W3136354265 date "2021-06-03" @default.
- W3136354265 modified "2023-10-14" @default.
- W3136354265 title "Exploring the room for repurposed hydroxychloroquine to impede COVID-19: toxicities and multipronged combination approaches with pharmaceutical insights" @default.
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