Morphometric Analysis of Temporal Bone Radiology for Cochlear Implant Candidacy.

Cochlear Implantation (CI) is a well-accepted treatment for severe-to-profound sensorineural hearing loss, refractory to conventional hearing amplification. Pre-operative Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) play pivotal roles in patient selection to rule out findings that preclude surgery or identify conditions that may impact the surgical procedure. A prospective study was carried out in a tertiary care center over three years, from January 2020 to January 2023. One hundred and ninety (380 ears) patients' High-Resolution Computed Tomography (HRCT) studies of the temporal bone and MRI scans of the auditory pathways were analyzed. A reporting format was followed which was devised by a team of senior implant surgeons and senior neuro-radiologists. Our study aims to provide a comprehensive radiologic protocol for CI candidacy including normative data for the essential morphometrics in the Indian setting.

SARS-CoV-2 variants infectivity prediction and therapeutic peptide design using computational approaches.

The outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2) has created a public health emergency globally. SARS-CoV-2 enters the human cell through the binding of the spike protein to human angiotensin converting enzyme 2 (ACE2) receptor. Significant changes have been reported in the mutational landscape of SARS-CoV-2 in the receptor binding domain (RBD) of S protein, subsequent to evolution of the pandemic. The present study examines the correlation between the binding affinity of mutated S-proteins and the rate of viral infectivity. For this, the binding affinity of SARS-CoV and variants of SARS-CoV-2 towards ACE2 was computationally determined. Subsequently, the RBD mutations were classified on the basis of the number of strains identified with respect to each mutation and the resulting variation in the binding affinity was computationally examined. The molecular docking studies indicated a significant correlation between the Z-Rank score of mutated S proteins and the rate of infectivity, suitable for predicting SARS-CoV-2 infectivity. Accordingly, a 30-mer peptide was designed and the inhibitory properties were computationally analyzed. Single amino acid-wise mutation was performed subsequently to identify the peptide with the highest binding affinity. Molecular dynamics and free energy calculations were then performed to examine the stability of the peptide-protein complexes. Additionally, selected peptides were synthesized and screened using a colorimetric assay. Together, this study developed a model to predict the rate of infectivity of SARS-CoV-2 variants and propose a potential peptide that can be used as an inhibitor for the viral entry to human.Communicated by Ramaswamy H. Sarma.

Potential protease inhibitors and their combinations to block SARS-CoV-2.

COVID-19, which has emerged recently as a pandemic viral infection caused by SARS-coronavirus 2 has spread rapidly around the world, creating a public health emergency. The current situation demands an effective therapeutic strategy to control the disease using drugs that are approved, or by inventing new ones. The present study examines the possible repurposing of existing anti-viral protease inhibitor drugs. For this, the structural features of the viral spike protein, the substrate for host cell protease and main protease of the available SARS CoV-2 isolates were established by comparing with related viruses for which antiviral drugs are effective. The results showed 97% sequence similarity among SARS and SARS-CoV-2 main protease and has same cleavage site positions and ACE2 receptor binding region as in the SARS-CoV spike protein. Though both are N-glycosylated, unlike SARS-CoV, human SARS-CoV-2 S-protein was O-glycosylated as well. Molecular docking studies were done to explore the role of FDA approved protease inhibitors to control SARS-CoV-2 replication. The results indicated that, Ritonavir has the highest potency to block SARS-CoV-2 main protease and human TMPRSS2, a host cell factor that aids viral infection. Other drugs such as Indinavir and Atazanavir also showed favourable binding with Cathepsin B/L that helped viral fusion with the host cell membrane. Further molecular dynamics simulation and MM-PBSA binding free energy calculations confirmed the stability of protein-drug complexes. These results suggest that protease inhibitors particularly Ritonavir, either alone or in combination with other drugs such as Atazanavir, have the potential to treat COVID 19.Communicated by Ramaswamy H. Sarma.

Delayed contrast enhancement in MRI in takotsubo cardiomyopathy.

We present a 21-year-old female whose clinical presentation and investigations were suggestive of takotsubo cardiomyopathy. On cardiac MRI, there was delayed gadolinium enhancement in apical and mid-segments with sparing of the base. Patient is in class III symptoms with ejection fraction of 24% at 1 year follow-up. This variant form of takotsubo cardiomyopathy with delayed contrast enhancement is associated with irreversible left ventricular dysfunction and poor outcome.