Abstract
Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, causes neonatal pig acute gastrointestinal infection with a characterization of severe diarrhea, vomiting, high morbidity, and high mortality, resulting in tremendous damages to the swine industry. Neither specific antiviral drugs nor effective vaccines are available, posing a high priority to screen antiviral drugs. The aim of this study is to investigate anti-PEDV effects of carbazole alkaloid derivatives. Eighteen carbazole derivatives (No.1 to No.18) were synthesized, and No.5, No.7, and No.18 were identified to markedly reduce the replication of enhanced green fluorescent protein (EGFP) inserted-PEDV, and the mRNA level of PEDV N. Flow cytometry assay, coupled with CCK8 assay, confirmed No.7 and No.18 carbazole derivatives displayed high inhibition effects with low cell toxicity. Furthermore, time course analysis indicated No.7 and No.18 carbazole derivatives exerted inhibition at the early stage of the viral life cycle. Collectively, the analysis underlines the benefit of carbazole derivatives as potential inhibitors of PEDV, and provides candidates for the development of novel therapeutic agents.
Highlights
Porcine epidemic diarrhea virus (PEDV) is an enveloped, single-stranded positivesense RNA virus that belongs to genera alphacoronavirus, the family Coronaviridae
The current feedback and vaccination protocols are frequently inefficient or unsafe, due to: no standardized protocol for feedback; poor capacities of current vaccines to induce lactogenic immunity; antigenic differences between vaccines with epidemic strains; possibility of continuous re-infection by PEDV used for feedback within herds; current live vaccines may revert to virulent PEDV or recombine with field PEDV strains to generate new strains after they are applied in the field [7,11,12,13,14,15]
Under the fluorescence microscopy observation, enhanced green fluorescent protein (EGFP) fluorescence was significantly reduced when PEDV-infected cells treated with No.5, No.7, or No.18 carbazole derivatives (Figure 2a)
Summary
Porcine epidemic diarrhea virus (PEDV) is an enveloped, single-stranded positivesense RNA virus that belongs to genera alphacoronavirus, the family Coronaviridae. PEDV can infect swine of all ages, with clinical symptoms including anorexia, vomiting, watery diarrhea, dehydration, and high mortality [3,4]. The immunization of pregnant sows is important in the control of epidemic PEDV, and in reducing the number of deaths in suckling piglets [7,9,10]. The most common practice was used to initiate herd immunity in US pig farms during the 2013–2017 epidemic when no PEDV vaccines were available [7,11]. There is an urgent need to find new methods to prevent and control PEDV
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