Összesen 2 találat.


001-es BibID:BIBFORM089444
035-os BibID:(cikkazonosító)190 (WOS)000595728400003 (Scopus)85096570971
Első szerző:Mahdi, Mohamed (orvos, tudományos segédmunkatárs)
Cím:Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2·s main protease / Mahdi Mohamed, Mótyán János András, Szojka Zsófia Ilona, Golda Mária, Miczi Márió, Tőzsér József
Megjegyzések:Background: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of infections worldwide. While the search for an effective antiviral is still ongoing, experimental therapies based on repurposing of available antivirals is being attempted, of which HIV protease inhibitors (PIs) have gained considerable interest. Inhibition profiling of the PIs directly against the viral protease has never been attempted in vitro, and while few studies reported an efficacy of lopinavir and ritonavir in SARS-CoV-2 context, the mechanism of action of the drugs remains to be validated. Methods We carried out an in-depth analysis of the efficacy of HIV PIs against the main protease of SARS-CoV-2 (Mpro) in cell culture and in vitro enzymatic assays, using a methodology that enabled us to focus solely on any potential inhibitory effects of the inhibitors against the viral protease. For cell culture experiments a dark-to-bright GFP reporter substrate system was designed. Results Lopinavir, ritonavir, darunavir, saquinavir, and atazanavir were able to inhibit the viral protease in cell culture, albeit in concentrations much higher than their achievable plasma levels, given their current drug formulations. While inhibition by lopinavir was attributed to its cytotoxicity, ritonavir was the most effective of the panel, with IC50 of 13.7 ?M. None of the inhibitors showed significant inhibition of SARS-CoV-2 Mpro in our in vitro enzymatic assays up to 100 ?M concentration. Conclusion Targeting of SARS-CoV-2 Mpro by some of the HIV PIs might be of limited clinical potential, given the high concentration of the drugs required to achieve significant inhibition. Therefore, given their weak inhibition of the viral protease, any potential beneficial effect of the PIs in COVID-19 context might perhaps be attributed to acting on other molecular target(s), rather than SARS-CoV-2 Mpro.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Inhibition profling
In vitro assay
HIV protease inhibitors
Megjelenés:Virology Journal. - 17 : 1 (2020), p. 1-8. -
További szerzők:Mótyán János András (1981-) (biokémikus, molekuláris biológus) Szojka Zsófia (1991-) (molekuláris biológus) Golda Mária (1986-) (molekuláris biológus) Miczi Márió Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész)
Pályázati támogatás:NKFIH-1150?6/2019
NKFI 125238
Internet cím:Szerző által megadott URL
Intézményi repozitóriumban (DEA) tárolt változat


001-es BibID:BIBFORM073421
Első szerző:Mahdi, Mohamed (orvos, tudományos segédmunkatárs)
Cím:Inhibitory effects of HIV-2 Vpx on replication of HIV-1 / Mohamed Mahdi, Zsófia Szojka, János András Mótyán, József Tőzsér
Megjegyzések:The human immunodeficiency viruses type 1 and 2 share a striking genomic resemblance, however, variability in the genetic sequence accounts for the presence of unique accessory genes; such as viral protein x (vpx) in HIV-2. Dual infection with both viruses has long been described in the literature, yet the molecular mechanism of how dually infected patients tend to do better than those who are mono-infected with HIV-1 has not yet been explored. We hypothesized that in addition to extracellular mechanisms, an HIV-2 accessory gene is the culprit, and interference at viral accessory/regulatory protein level is perhaps responsible for the attenuated pathogenicity of HIV-1 observed in dually infected patients. Following simulation of dual infection in cell culture experiments, we found that pre-transduction of cells with HIV-2 significantly protects against HIV-1 transduction. Importantly, we have found that this dampening of HIV-1's infectivity was a result of inter-viral interference carried out by the viral protein X of HIV-2, resulting in a severe hindrance to HIV-1's replication dynamics, influencing both its early- and late-phase of the viral life-cycle. Our findings shed light on potential intracellular interactions between the two viruses, and broaden our understanding of the observed clinical spectrum in dually infected patients, highlighting HIV-2 Vpx as a potential candidate worth exploring in the fight against HIV-1.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Virology. - 92 : 14 (2018), p. 1-46. -
További szerzők:Szojka Zsófia (1991-) (molekuláris biológus) Mótyán János András (1981-) (biokémikus, molekuláris biológus) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész)
Pályázati támogatás:125238
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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