In the present study, we propose Hyaluronic acid - 2-Deoxy-D-Glucose (HA-2DG) conjugate as a novel drug for the treatment of COVID-19. In silico molecular docking studies HA-2DG and 2-Deoxy-D-Glucose (2DG) against four different SARS-CoV-2 viral protein (Mpro, RdRp, PLpro and S protein) revealed that HA-2DG conjugate showed better binding affinity (-6.2, -7.2, -7.0 and 6.4 Kcal/mol) with all four screened SASR-CoV-2 viral targets than the antimetabolite drug 2DG alone (-4.8, -4.9, -4.6 and 4.7 Kcal/mol) respectively. ADMET analysis of 2DG and HA-2DG revealed that HA-2DG possessed reduced toxicity than 2DG alone. The study also revealed that the HA-2DG conjugate has multiple advantages of efficient drug delivery to its CD44 variant isoform receptors of the lower respiratory tract, highest interactive binding affinity with SARS-CoV-2 protein targets. Moreover, the HA-2DG drug conjugate possesses added advantages of good biodegradability, biocompatibility, no toxicity and non-immunogenicity. In conclusion, our study suggested that further in-vitro and in-vivo examination of HA-2DG drug conjugate will be useful to establish a promising early-stage antiviral drug for the novel treatment of COVID-19.
