Molecular insights of hyaluronic acid - ethambutol and hyaluronic acid - isoniazid drug conjugates act as promising novel drugs for the treatment of tuberculosis.

The present study examines cellular targeted drug delivery (CTDD) pattern of two novel Hyaluronic acid (HA) Tuberculosis Drug (TB) conjugates and its efficacy and strong binding affinity towards TB molecular protein targets. Two TB drugs ethambutol (EB) and isoniazid (IN) and their Hyaluronic acid conjugates (HA-EB & HA-IN) were tested for its metabolism, toxicity and excretion prediction through In silico tools they revealed hyaluronic acid conjugate of two TB drugs exhibited good drug profile over their free form of TB drugs. Further these four molecules subjected to In silico molecular docking study with four potential Mycobacterium tuberculosis target proteins (3PD8, 4Y0L, 5DZK and 6GAU). Molecular docking study revealed that hyaluronic conjugates (HA-EB & HA-IN) exhibit significant binding affinity and excellent docking scores with all screened molecular protein targets of TB over their free form of drug. Further molecular dynamic simulation was calculated for the four drug molecules (EB, IN, HA- EB & HA-IN) with DNA gyrase enzyme (PDB ID 6GAU) of Mycobacterium tuberculosis and the MDS results revealed that both the conjugates with the TB target protein possessed good number of interaction with binding pocket residues and good simulation scores than the free form of drugs.Communicated by Ramaswamy H. Sarma.

Molecular insights of hyaluronic acid-hydroxychloroquine conjugate as a promising drug in targeting SARS-CoV-2 viral proteins.

In-silico anti-viral activity of Hydroxychloroquine (HCQ) and its Hyaluronic Acid-derivative (HA-HCQ) towards different SARS-CoV-2 protein molecular targets were studied. Four different SARS-CoV-2 proteins molecular target i.e., three different main proteases and one helicase were chosen for In-silico anti-viral analysis. The HA-HCQ conjugates exhibited superior binding affinity and interactions with all the screened SAR-CoV-2 molecular target proteins with the exception of a few targets. The study also revealed that the HA-HCQ 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 target. Moreover, the HA-HCQ drug conjugate possesses added advantages of good biodegradability, biocompatibility, non-toxicity and non-immunogenicity. The prominent binding ability of HA-HCQ conjugate towards Mpro (PDB ID 5R82) and Helicase (PDB ID 6ZSL) target protein as compared with HCQ alone was proven through MD simulation analysis. In conclusion, our study suggested that further in-vitro and in-vivo examination of HA-HCQ drug conjugate will be useful to establish a promising early stage antiviral drug for the novel treatment of COVID-19.

Orbital multiple myeloma: case report and review of computed tomography features.

Orbital involvement at diagnosis in multiple myeloma is rare. Only a few a cases are reported with computed tomographic features. We report a case of orbital myeloma, and relevant medical reviews on computed tomography features are discussed.