Dataset Information

Natural Compound ZINC12899676 Reduces Porcine Epidemic Diarrhea Virus Replication by Inhibiting the Viral NTPase Activity.

ABSTRACT: Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus (α-CoV) that causes high mortality in suckling piglets, leading to severe economic losses worldwide. No effective vaccine or commercial antiviral drug is readily available. Several replicative enzymes are responsible for coronavirus replication. In this study, the potential candidates targeting replicative enzymes (PLP2, 3CLpro, RdRp, NTPase, and NendoU) were screened from 187,119 compounds in ZINC natural products library, and seven compounds had high binding potential to NTPase and showed drug-like property. Among them, ZINC12899676 was identified to significantly inhibit the NTPase activity of PEDV by targeting its active pocket and causing its conformational change, and ZINC12899676 significantly inhibited PEDV replication in IPEC-J2 cells. It first demonstrated that ZINC12899676 inhibits PEDV replication by targeting NTPase, and then, NTPase may serve as a novel target for anti-PEDV.

SUBMITTER: Wang P

PROVIDER: S-EPMC9114645 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Natural Compound ZINC12899676 Reduces Porcine Epidemic Diarrhea Virus Replication by Inhibiting the Viral NTPase Activity.

Wang Pengcheng P Wang Xianwei X Liu Xing X Sun Meng M Liang Xiao X Bai Juan J Jiang Ping P

Frontiers in pharmacology 20220504

Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus (α-CoV) that causes high mortality in suckling piglets, leading to severe economic losses worldwide. No effective vaccine or commercial antiviral drug is readily available. Several replicative enzymes are responsible for coronavirus replication. In this study, the potential candidates targeting replicative enzymes (PLP2, 3CLpro, RdRp, NTPase, and NendoU) were screened from 187,119 compounds in ZINC natural products library, and seven ...[more]

PMID: 35600889

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Project description:Chlamydiae may exist at the site of infection in an alternative replicative form, called the aberrant body (AB). ABs are produced during a viable but non-infectious developmental state termed "persistence" or "chlamydial stress." As persistent/stressed chlamydiae: (i) may contribute to chronic inflammation observed in diseases like trachoma; and (ii) are more resistant to current anti-chlamydial drugs of choice, it is critical to better understand this developmental stage. We previously demonstrated that porcine epidemic diarrhea virus (PEDV) co-infection induced Chlamydia pecorum persistence/stress in culture. One critical characteristic of persistence/stress is that the chlamydiae remain viable and can reenter the normal developmental cycle when the stressor is removed. Thus, we hypothesized that PEDV-induced persistence would be reversible if viral replication was inhibited. Therefore, we performed time course experiments in which Vero cells were C. pecorum/PEDV infected in the presence of cycloheximide (CHX), which inhibits viral but not chlamydial protein synthesis. CHX-exposure inhibited PEDV replication, but did not inhibit induction of C. pecorum persistence at 24 h post-PEDV infection, as indicated by AB formation and reduced production of infectious EBs. Interestingly, production of infectious EBs resumed when CHX-exposed, co-infected cells were incubated 48-72 h post-PEDV co-infection. These data demonstrate that PEDV co-infection-induced chlamydial persistence/stress is reversible and suggest that this induction (i) does not require viral replication in host cells; and (ii) does not require de novo host or viral protein synthesis. These data also suggest that viral binding and/or entry may be required for this effect. Because the PEDV host cell receptor (CD13 or aminopeptidase N) stimulates cellular signaling pathways in the absence of PEDV infection, we suspect that PEDV co-infection might alter CD13 function and induce the chlamydiae to enter the persistent state.

Dataset Information

Natural Compound ZINC12899676 Reduces Porcine Epidemic Diarrhea Virus Replication by Inhibiting the Viral NTPase Activity.

Publications

Natural Compound ZINC12899676 Reduces Porcine Epidemic Diarrhea Virus Replication by Inhibiting the Viral NTPase Activity.

Similar Datasets

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