Host-based Broad-spectrum Antiviral Drug Research

Viral infectious diseases pose a great threat to human health and affect economic development.Traditional antiviral drugs targeting viral RNA or viral proteins can cause mutations in the virus to cause drug resistance after long-term use,resulting in a decline in drug treatment effect or even loss of effect.Due to the large structural differences of different viruses,drugs designed to target viruses were difficult to produce broad-spectrum antiviral effects.Therefore,it is necessary to find a safe and effective broad-spectrum antiviral drug to cope with the new virus.The research of host-based antiviral drug provides a new method for the treatment of viral infectious diseases.By interfering with host cytokines to enhance the host cell immune response and then block the normal life cycle of pathogens in the host cells,the virus activity can be inhibited.Sialic acid which is a host cytokine widely existing in human body plays an important role in viral replication and transmission by mediating adhesion between the virus and host cells,cell signaling,etc.It was found that many viruses take sialic acid as their receptor and complete the replication cycle by interacting with sialic acid.AV5080 is a small molecule inhibitor based on sialic acid design.Pre-clinical studies have shown that AV5080 has significant antiviral activity in vitro and has good inhibitory effect on a variety of influenza viruses.It is possible that to obtain new broad-spectrum antiviral drugs by modifying the structure of AV5080.In this paper,the main contents of the study are as follows:(1)Based on AV5080 structure,Eight small molecules with similar structures were designed and screened through combinatorial chemistry and computer-aided drug design software ADMET and Sybyl.(2)(3R,4S,5S)-4,5-epoxy-3-(1-ethylpropoxy)-cyclohexene-1-ethyl carboxylate was used as raw material,twenty-four target compounds were synthesized by eight steps of ring opening,cyclization and acylation,etc.(3)he preliminary bioactivity of the 24 compounds was evaluated,and the SAR was analyzed according to bioactivityevaluation results.