De novo design of novel protease inhibitor candidates in the treatment of SARS-CoV-2 using deep learning, docking, and molecular dynamic simulations

The main protease of SARS-CoV-2 is a critical target for the design and development of antiviral drugs. 2.5 M compounds were used in this study to train an LSTM generative network via transfer learning in order to identify the four best candidates capable of inhibiting the main proteases in SARS-CoV-2. The network was fine-tuned over ten generations, with each generation resulting in higher binding affinity scores. The binding affinities and interactions between the selected candidates and the SARS-CoV-2 main protease are predicted using a molecular docking simulation using AutoDock Vina. The compounds selected have a strong interaction with the key MET 165 and Cys145 residues. Molecular dynamics (MD) simulations were run for 150ns to validate the docking results on the top four ligands. Additionally, root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and hydrogen bond analysis strongly support these findings. Furthermore, the MM-PBSA free energy calculations revealed that these chemical molecules have stable and favorable energies, resulting in a strong binding with Mpro's binding site. This study's extensive computational and statistical analyses indicate that the selected candidates may be used as potential inhibitors against the SARS-CoV-2 in-silico environment. However, additional in-vitro, in-vivo, and clinical trials are required to demonstrate their true efficacy

A Persian translation of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: psychometric properties.

The aim of this study is to assess the reliability and validity of a Persian translation of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders (SCID-I) through a multicenter study in a clinical population in Iran

Structured Clinical Interview for DSM-IV (SCID Persian Translation and Cultural Adaptation):

"nObjective: To translate the Structured Clinical Interview for DSM-IV axisI "ndisorders (SCID-I) into Persian (Farsi) and to adapt this instrument for the "nIranian culture. "nMethod: The SCID was translated into Persian using an elaborate procedure to "nachieve a satisfactory cross-cultural equivalent. This included forward "ntranslation by bilingual (English/Persian) translators, discussion and revision of "nthe translation in an expert panel of bilingual mental health professionals, pilot "nassessment on a small sample of Persian-speaking patients, back-translation "ninto English and comparison with the original SCID. In addition, "nunderstandability and acceptability of the translated items were assessed in 299 "npatients in three psychiatric hospitals in Tehran, Iran. "nResults: Some adaptations were made to bring about cross-cultural "ncomparability, especially with regard to conceptual differences which led to "ndifficulties in transferring some psychiatric concepts from English to Persian. "nThe SCID questions were generally understandable and acceptable for the "nIranian patients. "nConclusion: The SCID was translated into Persian in a multi-stage process to "nensure a satisfactory cross-cultural equivalent