Virology, Journal Year: 2024, Volume and Issue: 600, P. 110218 - 110218
Published: Sept. 3, 2024
Language: Английский
Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(11)
Published: May 31, 2023
There is a large global unmet need for the development of countermeasures to combat hundreds viruses known cause human disease and establishment therapeutic portfolio future pandemic preparedness. Most approved antiviral therapeutics target proteins encoded by single virus, providing narrow spectrum coverage. This, combined with slow pace high cost drug development, limits scalability this direct-acting (DAA) approach. Here, we summarize progress challenges in broad-spectrum antivirals that either viral elements (proteins, genome structures, lipid envelopes) or cellular proviral factors co-opted multiple via newly discovered compounds repurposing drugs. These strategies offer new means developing against both existing emerging threats complement DAAs.
Language: Английский
Citations
31
Journal of Virology, Journal Year: 2023, Volume and Issue: 97(8)
Published: Aug. 9, 2023
SARS-CoV-2 can enter cells after its spike protein is cleaved by either type II transmembrane serine proteases (TTSPs), like TMPRSS2, or cathepsins. It now widely accepted that the Omicron variant uses TMPRSS2 less efficiently and instead enters via cathepsins, but these findings have yet to be verified in more relevant cell models. Although we could confirm efficient cathepsin-mediated entry for a monkey kidney line, experiments with protease inhibitors showed (BA.1 XBB1.5) did not use cathepsins into human airway organoids utilized TTSPs. Likewise, CRISPR-edited intestinal of BA.1 relied on expression cathepsin L B. Together, data force us rethink concept has adapted indicate TTSP should dismissed as prophylactic therapeutic antiviral strategy against SARS-CoV-2. IMPORTANCE Coronavirus relies host activate viral fusion protein, spike. These determine route, tropism, range, attractive drug targets. Whereas earlier studies using lines suggested changed usage, from surface (TTSPs) endosomal report this case organoid models, suggesting inhibition still viable current variants highlighting importance vitro
Language: Английский
Citations
28
Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 75 - 75
Published: Jan. 7, 2025
TMPRSS2, a human transmembrane protease enzyme, plays crucial role in the spread of certain viruses, including influenza and coronaviruses. This enzyme promotes viral infection by cleaving glycoproteins, which helps viruses like SARS-CoV-2 A enter cells more effectively. Genetic differences TMPRSS2 may affect people’s susceptibility to COVID-19, underscoring need for studies that consider diverse populations. Beyond infectious diseases, has also been linked some cancers, suggesting it could be valuable target drug development. review provides summary inhibitors currently under study, with already clinical trials test their effectiveness against infections. As we uncover about TMPRSS2’s pathogenesis, open new doors therapies combat future outbreaks.
Language: Английский
Citations
1
Molecular Aspects of Medicine, Journal Year: 2022, Volume and Issue: 91, P. 101151 - 101151
Published: Oct. 28, 2022
With more than 5 million fatalities and close to 300 reported cases, COVID-19 is the first documented pandemic due a coronavirus that continues be major health challenge. Despite being rapid, uncontrollable, highly infectious in its spread, it also created incentives for technology development redefined public needs research agendas fast-track innovations translated. Breakthroughs computational biology peaked during with renewed attention making all cutting-edge deliver agents combat disease. The demand develop effective treatments yielded surprising collaborations from previously segregated fields of science technology. long-standing pharmaceutical industry's aversion repurposing existing drugs lack exponential financial gain was overrun by crisis pressures front-line researchers providers. Effective vaccine even at an unprecedented pace took year commence trials. Now emergence variants waning protections booster shots resulting breakthrough infections continue strain care systems. As now, every protein SARS-CoV-2 has been structurally characterized related host pathways have extensively mapped out. community addressed druggability multitude possible targets. This made virtual computer-assisted drug as well new tools technologies such artificial intelligence leads. Here this article, we are discussing advances discovery field target-based exploring implications known target-specific on therapeutic management. current scenario calls personalized medicine efforts stratifying patient populations early their need different combinations prognosis-specific therapeutics. We intend highlight target hotspots potential agents, ultimate goal using rational design therapeutics not only end but uncover generalizable platform use future pandemics.
Language: Английский
Citations
30
RSC Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 15(1), P. 81 - 118
Published: Oct. 13, 2023
In order to address the world-wide health challenge caused by COVID-19 pandemic, 3CL protease/SARS-CoV-2 main protease (SARS-CoV-2-M
Language: Английский
Citations
17
Clinical Microbiology and Infection, Journal Year: 2024, Volume and Issue: 30(6), P. 743 - 754
Published: Feb. 6, 2024
Language: Английский
Citations
6
Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 298 - 298
Published: Jan. 10, 2024
Background: In 2019, the breakthrough of coronavirus 2 disease (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS-CoV-2), represented one major issues our recent history. Different drugs have been tested to rapidly find effective anti-viral treatments and, among these, antiandrogens suggested play a role in mediating SARS-CoV-2 infection. Considering high heterogeneity studies on this topic, we decided review current literature. Methods: We performed systematic according PRISMA guidelines. A search strategy was conducted PUBMED and Medline. Only original articles published from March 2020 31 August 2023 investigating possible protective were included. vitro or preclinical reports not English language excluded. The main objective investigate how may interfere with COVID-19 outcomes. Results: Among 1755 records, selected studies, majority which consisted retrospective clinical data collections randomized trials during first second wave pandemic. Conclusions: conclusion, can state that do seem protect individuals infection severity thus, their use should be encouraged field.
Language: Английский
Citations
5
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 11173 - 11173
Published: July 6, 2023
Aprotinin (APR) was discovered in 1930. APR is an effective pan-protease inhibitor, a typical "magic shotgun". Until 2007, widely used as antithrombotic and anti-inflammatory drug cardiac noncardiac surgeries for reduction of bleeding thus limiting the need blood transfusion. The ability to inhibit proteolytic activation some viruses leads its use antiviral prevention treatment acute respiratory virus infections. However, due incompetent interpretation several clinical trials followed by incredible controversy literature, usage nearly stopped decade worldwide. In 2015-2020, after re-analysis these trials' data restrictions were lifted This review discusses mechanisms action summarizes current knowledge prospective regarding diseases caused RNA-containing viruses, including influenza SARS-CoV-2 or part combination treatment.
Language: Английский
Citations
11
Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10
Published: Nov. 2, 2023
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants virus have further exacerbated COVID-19 mortality and infection rates, emphasizing urgent need for effective preventive strategies. Understanding viral mechanism crucial developing therapeutics vaccines. The entry SARS-CoV-2 into host cells key step in pathway has been targeted drug development. Despite numerous reviews virus, there lack comprehensive focusing on structural aspects entry. In this review, we analyze changes Spike proteins during process, dividing process prebinding, receptor binding, proteolytic cleavage, membrane fusion steps. By understanding atomic-scale details entry, can better target intervention We also examine impacts mutations proteins, including Omicron variant, Structural information provides insights effects guide development Finally, discuss available structure-based approaches Overall, review detailed analysis highlighting its significance vaccines against COVID-19. Therefore, our emphasizes importance combating infection.
Language: Английский
Citations
10
Antiviral Research, Journal Year: 2025, Volume and Issue: 235, P. 106101 - 106101
Published: Feb. 7, 2025
The global response to the COVID-19 pandemic, caused by novel SARS-CoV-2 virus, has seen an unprecedented increase in development of antiviral therapies. Traditional strategies have primarily focused on direct-acting antivirals (DAAs), which specifically target viral components. In recent years, increasing attention was given alternative approach aiming exploit host cellular pathways or immune responses inhibit replication, led so-called host-targeted (HTAs). emergence and promoted a boost this field. Numerous HTAs been tested demonstrated their potential against through vitro vivo studies. However, striking contrast, only limited number successfully progressed advanced clinical trial phases (2-4), even less entered practice. This review aims explore current landscape targeting that reached phase 2-4 trials. Additionally, it will challenges faced gaining regulatory approval market availability.
Language: Английский
Citations
0