Small molecules in the treatment of COVID-19

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Дек. 5, 2022

Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies economies. Until now, effective therapeutics against are in high demand. Along with our improved understanding the structure, function, pathogenic process SARS-CoV-2, many small molecules potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition viral proteins such as RdRp M pro , interference host enzymes including ACE2 proteases, blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, NLRP3 pathways, regarded feasible drug development. development treat achieved strategies, computer-aided lead compound design screening, natural product discovery, repurposing, combination therapy. Several representative remdesivir paxlovid proved or authorized emergency use countries. And candidates entered clinical-trial stage. Nevertheless, due epidemiological features variability issues it is necessary continue exploring novel COVID-19. This review discusses current findings for treatment. Moreover, their detailed mechanism action, chemical structures, preclinical clinical efficacies discussed.

Язык: Английский

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Effects of COVID‐19 vaccination during pregnancy on SARS‐CoV‐2 infection and maternal and neonatal outcomes: A systematic review and meta‐analysis

Reviews in Medical Virology, Год журнала: 2023, Номер 33(3)

Опубликована: Март 10, 2023

SARS-CoV-2 infection during pregnancy is associated with adverse maternal and neonatal outcomes, but no systematic synthesis of evidence on COVID-19 vaccination against these outcomes has been undertaken. Thus, we aimed to assess the collective effects outcomes. PubMed/MEDLINE, CENTRAL, EMBASE were systematically searched for articles published up 1 November 2022. A review meta-analysis performed calculate pooled size 95% confidence interval (CI). We evaluated 30 studies involving 862,272 individuals (308,428 vaccinated 553,844 unvaccinated). Overall analyses in pregnant women showed reduced risks by 60% (41%-73%), hospitalisation 53% (31%-69%), intensive care unit (ICU) admission 82% (12%-99%). Neonates 1.78 folds more likely acquire first 2, 4 6 months life Omicron period. The risk stillbirth was 45% (17%-63%) association (vs. vaccination) pregnancy. decrease 15% (3%-25%), 33% (14%-48%), (17%-46%) odds preterm births before 37, 32 28 weeks' gestation pregnancy, respectively. ICU significantly lower 20% following (16%-24%). There a higher including miscarriage, gestational diabetes, hypertension, cardiac problems, oligohydramnios, polyhydramnios, unassisted vaginal delivery, cesarean postpartum haemorrhage, age at placental abruption, Apgar score 5 min below 7, low birthweight (<2500 g), very (<1500 small age, foetal abnormalities. safe highly effective preventing without increasing reduction stillbirth, births, admission. Importantly, did not reduce

Язык: Английский

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COVID-19 drug discovery and treatment options

Nature Reviews Microbiology, Год журнала: 2024, Номер 22(7), С. 391 - 407

Опубликована: Апрель 15, 2024

Язык: Английский

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Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2—A narrative review

Journal of Medical Virology, Год журнала: 2022, Номер 94(7), С. 3006 - 3016

Опубликована: Март 22, 2022

Broad-spectrum antiviral agents targeting viral RNA-dependent RNA polymerase (RdRp) are expected to be a key therapeutic strategy in the ongoing coronavirus disease 2019 (COVID-19) pandemic and its future variants of severe acute respiratory syndrome 2 (SARS-CoV-2), virus that causes COVID-19. Molnupiravir is nucleoside analog vivo experiments have been reported inhibit replication SARS-CoV-2, Clinical trials molnupiravir as therapy for patients with mild-to-moderate COVID-19 also suggest significant efficacy comparison placebo. lethally mutagenic against RNA, but effect on host cell DNA being questioned. Herein, safety concerns discussed recent findings from published reports clinical trials. The unchanged mutated SARS-CoV-2 highlighted. With administration via oral route, turn tide pandemic.

Язык: Английский

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Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies

Journal of Medical Virology, Год журнала: 2022, Номер 95(1)

Опубликована: Ноя. 14, 2022

Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The can result in flu-like symptoms, fever, and persistent rash. currently spreading throughout world prevention treatment efforts are being intensified. Although there no that has been specifically approved for virus infection, infected patients may benefit from using certain antiviral medications typically prescribed of smallpox. drugs tecovirimat, brincidofovir, cidofovir, all which short supply due to spread Resistance also concern, as widespread replication lead mutations produce viruses resistant available treatments. This article discusses disease, potential drug targets, management strategies overcome disease. With discovery new drugs, it hoped problem insufficient will be resolved, not anticipated resistance become major issue near future.

Язык: Английский

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Repurposing Molnupiravir for COVID-19: The Mechanisms of Antiviral Activity

Viruses, Год журнала: 2022, Номер 14(6), С. 1345 - 1345

Опубликована: Июнь 20, 2022

Molnupiravir is a β-d-N4-hydroxycytidine-5′-isopropyl ester (NHC) compound that exerts antiviral activity against various RNA viruses such as influenza, SARS, and Ebola viruses. Thus, the repurposing of has gained significant attention for combatting infection with SARS-CoV-2, etiological agent COVID-19. Recently, was granted authorization treatment mild-to-moderate COVID-19 in adults. Findings from vitro experiments, vivo studies clinical trials reveal effective SARS-CoV-2 by inducing viral mutagenesis, thereby giving rise to mutated complementary strands generate non-functional To date, data collectively suggest possesses promising well favorable prophylactic efficacy, attributed its mutagenic property disrupting replication. This review discusses mechanisms action highlights utility disabling replication, ameliorating severity. Despite relatively few short-term adverse effects thus far, further detailed long-term pharmacovigilance are needed view effects.

Язык: Английский

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Efficacy and safety of tixagevimab‐cilgavimab as pre‐exposure prophylaxis for COVID‐19: A systematic review and meta‐analysis

Reviews in Medical Virology, Год журнала: 2023, Номер 33(2)

Опубликована: Янв. 8, 2023

Abstract Some proportions of populations, such as immunocompromised patients and organ transplant recipients might have inadequate immune responses to the vaccine for coronavirus disease 2019 (COVID‐19). For these groups administering monoclonal antibodies offer some additional protection. This review sought analyze effectiveness safety tixagevimab‐cilgavimab (Evusheld) pre‐exposure prophylaxis against COVID‐19. We used specific keywords comprehensively search potential studies on PubMed, Scopus, Europe PMC, ClinicalTrials.gov sources until 3 September 2022. collected all published articles that analyzed course Review Manager 5.4 was utilized statistical analysis. Six were included. Our pooled analysis revealed may decrease rate SARS‐CoV‐2 infection (OR: 0.24; 95% CI: 0.15–0.40, p < 0.00001, I 2 = 75%), lower COVID‐19 hospitalization 0.13; 0.07–0.24, 0%), severity risk deaths 0.17; 0.03–0.99, 0.05, 72%). In included studies, no major adverse events reported. study proposes effective safe preventing Tixagevimab‐cilgavimab be offered those who cannot vaccinated or response from give

Язык: Английский

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Antiviral Molecular Targets of Essential Oils against SARS-CoV-2: A Systematic Review

Scientia Pharmaceutica, Год журнала: 2023, Номер 91(1), С. 15 - 15

Опубликована: Март 6, 2023

Essential oils are potential therapeutics for coronavirus disease 2019 (COVID-19), in which some of the volatile compounds essential have been well known their broad antiviral activities. These therapeutic candidates shown to regulate excessive secretion pro-inflammatory cytokines, underlies pathogenesis severe COVID-19. We aimed identify molecular targets disrupting cell entry and replication SARS-CoV-2, hence being active as antivirals. Literature searches were performed on PubMed, Scopus, Scillit, CaPlus/SciFinder (7 December 2022) with a truncated title implying anti-SARS-CoV-2 activity oil. Data collected from eligible studies described narratively. Quality appraisal was included studies. A total eight this review; four used enzyme inhibition assay, one—pseudo-SARS-CoV-2 culture; two—whole SARS-CoV-2 one—ACE2-expressing cancer cells. may prevent infection by targeting its receptors cells (ACE2 TMPRSS2). Menthol, 1,8-cineole, camphor among serve ACE2 blockers. β-caryophyllene selectively target spike protein inhibit viral entry. Other interactions proteases RdRp observed based docking. In conclusion, could proteins related replication. Further improved uniform study designs should be carried out optimize COVID-19 therapies.

Язык: Английский

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Quercetin for the treatment of COVID‐19 patients: A systematic review and meta‐analysis

Reviews in Medical Virology, Год журнала: 2023, Номер 33(2)

Опубликована: Фев. 13, 2023

Abstract Currently approved therapies for COVID‐19 are mostly limited by their low availability, high costs or the requirement of parenteral administration trained medical personnel in an in‐hospital setting. Quercetin is a cheap and easily accessible therapeutic option patients. However, it has not been evaluated systematic review until now. We aimed to conduct meta‐analysis assess effect quercetin on clinical outcomes Various databases including PubMed, Cochrane Library Embase were searched from inception 5 October 2022 results six randomized controlled trials (RCTs) pooled using random‐effects model. All analyses conducted RevMan 5.4 with odds ratio (OR) as measure. decreased risk intensive care unit admission (OR = 0.31; 95% confidence interval (CI) 0.10–0.99) incidence hospitalisation 0.25; CI 0.10–0.62) but did decrease all‐cause mortality rate no recovery. may be benefit patients, especially if administered its phytosome formulation which greatly enhances bioavailability large‐scale RCTs needed confirm these findings.

Язык: Английский

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Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval

Journal of Korean Medical Science, Год журнала: 2024, Номер 39(14)

Опубликована: Янв. 1, 2024

The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing have been repurposed new drugs emerged. Here we summarize mechanisms clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data vaccines drugs, as well developmental pipelines, using databases from the following organizations: United States Food Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical Medical Devices (PMDA), ClinicalTrials.gov. In all, 387 were found initial review. After removing unrelated 66 selected, including 17 49 under These classified into six categories: 1) targeting viral life cycle 2) Anti-severe acute respiratory syndrome 2 Monoclonal Antibodies, 3) immunomodulators, 4) anti-coagulants, 5) COVID-19-induced neuropathy 6) other therapeutics. Among development are following: 6 cycle, 12 immunosuppression immunostimulants, HIF-PHD 3 GM-CSF 5 others. This review provides insight action, properties, indications medications.

Язык: Английский

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