Middle East Respiratory Syndrome (MERS) is a viral respiratory illness caused by a novel coronavirus (MERS-CoV) which was identified in Saudi Arabia in 2012 [
1,
2]. Up to December 2016, the mortality rate of MERS patients is 35.4% with 652 deaths out of 1842 confirmed cases [
3]. There is still no effective anti-MERS medicine or vaccine commercially available in the market. One previous study showed that stilbene derivatives could contain antiviral activities against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) [
4]. As a result, we tested whether a natural stilbene derivative, resveratrol (
trans-3, 5, 4′-trihydroxystilbene) inhibits the MERS-CoV infection in this study. Resveratrol exists widely in different plants, including grape
(Vitis vinifera), Huzhang (
Polygonum cuspidatum) and cranberry (
Vaccinium macrocarpon)[
5]. In the past, resveratrol was demonstrated to decrease the production of nitric oxide in tissue, and thereby reduce inflammation [
6‐
8]. Resveratrol also acts as an antioxidant to remove free radicals [
9,
10], thus restrains tumor growth [
11] and even age-related diseases [
12,
13]. Resveratrol also inhibits STAT3 signaling pathway [
14], the mTOR signaling [
15], and the hedgehog signaling pathway [
16]. Furthermore, resveratrol reportedly constrains infections caused by multiple pathogens, such as
Helicobacter pylori [
17],
Staphylococcus aureus [
18] or
Toxoplasma gondii [
19]. Interestingly, resveratrol has been demonstrated to exert antiviral effects against various viral infections, including Epstein-Barr virus (EBV) [
20,
21], enterovirus 71 (EV71) [
22], and herpes simplex virus (HSV) [
23], as well as respiratory viral infections caused by influenza [
24], respiratory syncytial virus (RSV) [
25,
26], and rhinovirus [
27]. However, it remains unknown whether resveratrol can inhibit MERS-CoV infection. In this study, we evaluated the antiviral effectiveness of resveratrol against MERS-CoV with an
in vitro model.