In Vitro Replication Inhibitory Activity of Xanthorrhizol against Severe Acute Respiratory Syndrome Coronavirus 2

Abstract

In spite of the large number of repositioned drugs and direct-acting antivirals in clinical trials for the management of the ongoing COVID-19 pandemic, there are few cost-effective therapeutic options for severe acute respiratory syndrome (SARS) coronavirus 2 (SCoV2) infection. In this paper, we show that xanthorrhizol (XNT), a bisabolane-type sesquiterpenoid compound isolated from the Curcuma xanthorrhizza Roxb., a ginger-line plant of the family Zingiberaceae, displays a potent antiviral efficacy in vitro against SCoV2 and other related coronaviruses, including SARS-CoV-1 (SCoV1) and a common cold-causing human coronavirus. XNT reduced infectious SCoV2 titer by ~3-log10 at 20 μM and interfered with the replication of the SCoV1 subgenomic replicon, while it had no significant antiviral effects against hepatitis C virus and noroviruses. Further, XNT exerted similar antiviral functions against SCoV2 variants, such as a GH clade strain and a delta strain currently predominant worldwide. Neither SCoV2 entry into cells nor the enzymatic activity of viral RNA polymerase (Nsp12), RNA helicase (Nsp13), or the 3CL main protease (Nsp5) was inhibited by XNT. While its CoV replication inhibitory mechanism remains elusive, our results demonstrate that the traditional folk medicine XNT could be a promising antiviral candidate that inhibits a broad range of SCoV2 variants of concern and other related CoVs.

Enhanced Omicron subvariant cross-neutralization efficacy of a monovalent SARS-CoV-2 BA.4/5 mRNA vaccine encoding a noncleaved, nonfusogenic spike antigen

“…no. QPK-101) as described previously 41 . Pseudovirus genome copy number was quantified using RT-qPCR.…”

Prospective Medicinal Plants and Their Phytochemicals Shielding Autoimmune and Cancer Patients Against the SARS-CoV-2 Pandemic: A Special Focus on Matcha

“…Xanthorrhizol was shown to have a potent antiviral activity against SARS-CoV-2 variants such as GH clade strain and delta strain, so it can be a promising antiviral plant against COVID-19 ( 241 ).…”

Influence of Zika virus 3′-end sequence and nonstructural protein evolution on the viral replication competence and virulence

“…In vitro RdRp assay was performed as described previously [ 35 ]. Briefly, 5 pmol of recombinant ZIKV NS5 in a total volume of 25 µl reaction buffer [50 mM Tris-HCl (pH 8.0), 50 mM NaCl, 2.5 mM MnCl 2 , 1 mM DTT, 10% glycerol, and 20 units of RNase inhibitor] containing 1 µg of poly(A) RNA template, 5 µM complementary rUTP, 5 µCi [α- 32 P] of rUTP (3.000 Ci/mmol, Amersham Pharmacia Biotech).…”

“…ZIKV prME protein-pseudotyped MLV expressing nanoluciferase was generated as previously described [ 35 , 38 ]. Briefly, HEK293T cells were transfected with pUMVC, pBABE-puro-NanoLuc, and a mammalian vector expressing the ZIKV CaprME.…”