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      In Vitro Inhibition of Alphaviruses by Lycorine

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          Abstract

          Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. As an emerging virus, CHIKV imposes a threat to public health. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. Lycorine, an alkaloid from Amaryllidaceae plants, has antiviral activity against a number of viruses such as coronavirus, flavivirus and enterovirus. In this study, we found that lycorine could inhibit CHIKV in cell culture at a concentration of 10 μmol/L without apparent cytotoxicity. In addition, it exhibited broad-spectrum anti-alphavirus activity, including Sindbis virus (SINV), Semliki Forest virus (SFV), and Venezuelan equine encephalomyelitis virus (VEEV). The time of addition studies indicated that lycorine functions at an early post-entry stage of CHIKV life cycle. The results based on two different CHIKV replicons provided further evidence that lycorine exerts its antiviral activity mainly by inhibiting CHIKV translation. Overall, our study extends the antiviral spectrum of lycorine.

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          High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses

          Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs in vitro. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.
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            Biology and pathogenesis of chikungunya virus.

            Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus responsible for a recent, unexpectedly severe epidemic in countries of the Indian Ocean region. Although many alphaviruses have been well studied, little was known about the biology and pathogenesis of CHIKV at the time of the 2005 outbreak. Over the past 5 years there has been a multidisciplinary effort aimed at deciphering the clinical, physiopathological, immunological and virological features of CHIKV infection. This Review highlights some of the most recent advances in our understanding of the biology of CHIKV and its interactions with the host.
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              Viral RNA structure-based strategies to manipulate translation

              Viruses must co-opt the cellular translation machinery to produce progeny virions. Eukaryotic viruses have evolved a variety of ways to manipulate the cellular translation apparatus, in many cases using elegant RNA-centred strategies. Viral RNAs can alter or control every phase of protein synthesis and have diverse targets, mechanisms and structures. In addition, as cells attempt to limit infection by downregulating translation, some of these viral RNAs enable the virus to overcome this response or even take advantage of it to promote viral translation over cellular translation. In this Review, we present important examples of viral RNA-based strategies to exploit the cellular translation machinery. We describe what is understood of the structures and mechanisms of diverse viral RNA elements that alter or regulate translation, the advantages that are conferred to the virus and some of the major unknowns that provide motivation for further exploration.
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                Author and article information

                Contributors
                zhangbo@wh.iov.cn
                shanglq@nankai.edu.cn
                yehq@wh.iov.cn
                Journal
                Virol Sin
                Virol Sin
                Virologica Sinica
                Springer Singapore (Singapore )
                1674-0769
                1995-820X
                10 August 2021
                : 1-10
                Affiliations
                [1 ]GRID grid.439104.b, ISNI 0000 0004 1798 1925, Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, , Wuhan Institute of Virology, Chinese Academy of Sciences, ; Wuhan, 430071 China
                [2 ]GRID grid.216938.7, ISNI 0000 0000 9878 7032, College of Pharmacy and Drug Discovery Center for Infectious Diseases, , Nankai University, ; Tianjin, 300350 China
                Author information
                http://orcid.org/0000-0002-8895-3679
                http://orcid.org/0000-0003-4424-3162
                http://orcid.org/0000-0001-7770-4071
                Article
                438
                10.1007/s12250-021-00438-z
                8353614
                34374926
                b5572506-60a3-47c0-94e1-aba005a9dca7
                © Wuhan Institute of Virology, CAS 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 8 May 2021
                : 8 June 2021
                Categories
                Research Article

                chikungunya virus (chikv),alphavirus,lycorine,antiviral
                chikungunya virus (chikv), alphavirus, lycorine, antiviral

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