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Curr Top Med Chem ; 20(11): 915-962, 2020.
Article in English | MEDLINE | ID: covidwho-1453165


BACKGROUND: Emerging viral zoonotic diseases are one of the major obstacles to secure the "One Health" concept under the current scenario. Current prophylactic, diagnostic and therapeutic approaches often associated with certain limitations and thus proved to be insufficient for customizing rapid and efficient combating strategy against the highly transmissible pathogenic infectious agents leading to the disastrous socio-economic outcome. Moreover, most of the viral zoonoses originate from the wildlife and poor knowledge about the global virome database renders it difficult to predict future outbreaks. Thus, alternative management strategy in terms of improved prophylactic vaccines and their delivery systems; rapid and efficient diagnostics and effective targeted therapeutics are the need of the hour. METHODS: Structured literature search has been performed with specific keywords in bibliographic databases for the accumulation of information regarding current nanomedicine interventions along with standard books for basic virology inputs. RESULTS: Multi-arrayed applications of nanomedicine have proved to be an effective alternative in all the aspects regarding the prevention, diagnosis, and control of zoonotic viral diseases. The current review is focused to outline the applications of nanomaterials as anti-viral vaccines or vaccine/drug delivery systems, diagnostics and directly acting therapeutic agents in combating the important zoonotic viral diseases in the recent scenario along with their potential benefits, challenges and prospects to design successful control strategies. CONCLUSION: This review provides significant introspection towards the multi-arrayed applications of nanomedicine to combat several important zoonotic viral diseases.

Drug Delivery Systems/methods , Viral Vaccines/chemistry , Viral Zoonoses/diagnosis , Viral Zoonoses/prevention & control , Viral Zoonoses/therapy , Viruses/drug effects , Animals , Animals, Wild , Biosensing Techniques , Drug Carriers/chemistry , Drug Compounding , Drug Liberation , Humans , Nanomedicine , Nanoparticles/chemistry , Polymers/chemistry , Polymers/metabolism , Transfection , Viruses/metabolism
Angew Chem Int Ed Engl ; 60(29): 15870-15878, 2021 07 12.
Article in English | MEDLINE | ID: covidwho-1265369


Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with an IC50 of 67 µg mL-1 (approx. 1.6 µm). This synthetic polysulfate exhibits more than 60-fold higher virus inhibitory activity than heparin (IC50 : 4084 µg mL-1 ), along with much lower anticoagulant activity. Furthermore, in molecular dynamics simulations, we verified that LPGS can bind more strongly to the spike protein than heparin, and that LPGS can interact even more with the spike protein of the new N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into host cells can be blocked via electrostatic interactions, therefore LPGS can serve as a blueprint for the design of novel viral inhibitors of SARS-CoV-2.

Antiviral Agents/metabolism , Heparin/metabolism , Pentosan Sulfuric Polyester/metabolism , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects , A549 Cells , Animals , Antiviral Agents/chemistry , Chlorocebus aethiops , Heparin/chemistry , Humans , Molecular Dynamics Simulation , Pentosan Sulfuric Polyester/chemistry , Polymers/chemistry , Polymers/metabolism , Protein Binding , Spike Glycoprotein, Coronavirus/chemistry , Static Electricity , Vero Cells