Obsessive-Compulsive Disorder (OCD): A Comprehensive Review of Diagnosis, Comorbidities, and Treatment Approaches.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder widely recognized for its recurrent obsessions and compulsions, which may cause severe impairment worldwide. This review explores the difficulties in diagnosing OCD, its comorbidities, and its treatment approaches. Psychiatry and neuroscience face noteworthy obstacles in treating OCD, which is frequently misdiagnosed and inadequately addressed. This illness, which causes upsetting symptoms that interfere with day-to-day living, affects not only adults but also children and adolescents to a great extent. Despite the availability of multiple therapy methods, such as pharmacological and psychological approaches, many patients exhibit resistance, emphasizing the necessity for alternative therapies. OCD and other psychiatric conditions like bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder substantially overlap, highlighting the complexity of mental health diagnoses. Furthermore, its comorbidity with these diseases further highlights OCD's intricacy. Several therapy considerations have been mentioned, such as using larger dosages of medications and combining different therapeutic approaches. Their association suggests possible common pathogenic pathways between OCD and other psychiatric illnesses. The review concludes that, given the significant number of people who still struggle with chronic symptoms, new treatment techniques and ongoing research are necessary, even in the face of improvements in the understanding and treatment of OCD.

Sliding of HIV-1 reverse transcriptase over DNA creates a transient P pocket - targeting P-pocket by fragment screening.

HIV-1 reverse transcriptase (RT) slides over an RNA/DNA or dsDNA substrate while copying the viral RNA to a proviral DNA. We report a crystal structure of RT/dsDNA complex in which RT overstepped the primer 3'-end of a dsDNA substrate and created a transient P-pocket at the priming site. We performed a high-throughput screening of 300 drug-like fragments by X-ray crystallography that identifies two leads that bind the P-pocket, which is composed of structural elements from polymerase active site, primer grip, and template-primer that are resilient to drug-resistance mutations. Analogs of a fragment were synthesized, two of which show noticeable RT inhibition. An engineered RT/DNA aptamer complex could trap the transient P-pocket in solution, and structures of the RT/DNA complex were determined in the presence of an inhibitory fragment. A synthesized analog bound at P-pocket is further analyzed by single-particle cryo-EM. Identification of the P-pocket within HIV RT and the developed structure-based platform provide an opportunity for the design new types of polymerase inhibitors.