Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase

COVID-19 has become a global public health crisis since its outbreak in China in December 2019.Currently there are few clinically effective drugs to combat SARS-CoV-2 infection.The main protein(M^(pro)),papain-like protease(PL^(pro))and RNA-dependent RNA polymerase(RdRp)of SARS-CoV-2 are involved in the viral replication,and might be prospective targets for anti-coronavirus drug development.Here,we investigated the antiviral activity of oridonin,a natural small-molecule compound,against SARS-CoV-2 infection in vitro.The time-of-addition analysis showed that oridonin efficiently inhibited SARS-CoV-2 infection by interfering with the genome replication at the post-entry stage.Mechanistically,the inhibition of viral replication by oridonin depends on the oxidation activity ofα,β-unsaturated carbonyl.Further experiments showed that oridonin not only effectively inhibited SARS-CoV-2 Mpro activity,but also had some inhibitory effects on PLpro-mediated deubiquitinating and viral polymerase-catalyzed RNA elongation activities at high concentrations.In particular,oridonin could inhibit the bat SARS-like CoV and the newly emerged SARS-CoV-2 omicron variants(BA.1 and BA.2),which highlights its potential as a pan-coronavirus antiviral agent.Overall,our data provide strong evidence that oridonin is an efficient antiviral agent against SARS-CoV-2 infection.

On the Lie Algebras, Generalized Symmetries and Darboux Transformations of the Fifth-Order Evolution Equations in Shallow Water

By considering the one-dimensional model for describing long, small amplitude waves in shallow water, a generalized fifth-order evolution equation named the Olver water wave(OWW) equation is investigated by virtue of some new pseudo-potential systems. By introducing the corresponding pseudo-potential systems, the authors systematically construct some generalized symmetries that consider some new smooth functions{Xiβ}i=1,2,···,nβ =1,2,···,N depending on a finite number of partial derivatives of the nonlocal variables vβand a restriction ∑iα,β(? ξi/?vβ)2+(?ηα/?vβ)2≠0, i.e.,∑i,α,β(?Gα/?vβ)2≠0. Furthermore,the authors investigate some structures associated with the Olver water wave(AOWW)equations including Lie algebra and Darboux transformation. The results are also extended to AOWW equations such as Lax, Sawada-Kotera, Kaup-Kupershmidt, It and Caudrey-Dodd-Gibbon-Sawada-Kotera equations, et al. Finally, the symmetries are applied to investigate the initial value problems and Darboux transformations.