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}β=1,2…,N^i=1,2…,n depending on a finite number of partial derivatives of the nonlocal variables vβ and a restriction i,α,β∑（ ξi/ vβ）^2＋（ ηα/ vβ）^2≠0,ie.,i,α,β∑（ ξi/ vβ）^2≠0. Furthermore, i,a,B i,a,~ 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, It6 and Caudrey-Dodd-Cibbon-Sawada-Kotera equations, et al. Finally, the symmetries are ap- plied to investigate the initial value problems and Darboux transformations.