Dihydroorotate dehydrogenase (DHODH) is a key enzyme required for de novo pyrimidine synthesis and it is suggested as a target for COVID19 treatment due to high pyrimidine demand by the virus replication in the infected host cells as well as its proven effect of blocking of cytokine release by the immune cells to prevent inflammation leading to acute respiratory distress. There are a number of clinical trials underway for COVID19 treatment using DHODH inhibitors; however, there are only a small number of known DHODH antagonists available for testing. Here, we have applied a methodology to identify DHODH antagonist candidates, and compared them using in silico target prediction tools. A large set of 7900 FDA-approved and clinical stage drugs obtained from DrugBank were docked against 20 different structures DHODH available in PDB. Drugs were eliminated according to their predicted affinities by Autodock Vina. About 28 FDA-approved and 79 clinical trial ongoing drugs remained. The mode of interaction of these molecules was analyzed by repeating docking using Autodock 4 and DS Visualiser. Finally, the target region predictions of 28 FDA-approved drugs were determined through PASS and SwissTargetPrediction tools. Interestingly, the analysis of in silico target predictions revealed that serotonin-dopamine receptor antagonists could also be potential DHODH inhibitors. Our candidates shared a common attribute, a possible interaction with serotonin-dopamine receptors as well as other oxidoreductases, like DHODH. Moreover, the Bruton Tyrosine Kinase-inhibitor acalabrutunib and serotonin-dopamine receptor inhibitor drugs on our list have been found in the literature that have shown to be effective against Sars-CoV-2, while the path of activity is yet to be identified. Identifying an effective drug that can suppress both inflammation and virus proliferation will play a crucial role in the treatment of COVID. Therefore, we suggest experimental investigation of the 28 FDA-approved drugs on DHODH activity and Sars-CoV-2 virus proliferation. Those who are found experimentally effective can play an important role in COVID19 treatment. Moreover, we suggest investigating COVID19 case conditions in patients using schizophrenia and depression drugs.
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http://dx.doi.org/10.1093/bib/bbaa379 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139.
Protein language models (PLMs) have demonstrated impressive success in modeling proteins. However, general-purpose "foundational" PLMs have limited performance in modeling antibodies due to the latter's hypervariable regions, which do not conform to the evolutionary conservation principles that such models rely on. In this study, we propose a transfer learning framework called Antibody Mutagenesis-Augmented Processing (AbMAP), which fine-tunes foundational models for antibody-sequence inputs by supervising on antibody structure and binding specificity examples.
View Article and Find Full Text PDFJMIR Res Protoc
January 2025
UK Health Security Agency, London, United Kingdom.
Background: Due to advances in treatment, HIV is now a chronic condition with near-normal life expectancy. However, people with HIV continue to have a higher burden of mental and physical health conditions and are impacted by wider socioeconomic issues. Positive Voices is a nationally representative series of surveys of people with HIV in the United Kingdom.
View Article and Find Full Text PDFJ Med Internet Res
January 2025
Department of Psychiatry, Yongin Severance Hospital, Yongin, Republic of Korea.
Background: The COVID-19 pandemic has accelerated the digitalization of modern society, extending digital transformation to daily life and psychological evaluation and treatment. However, the development of competencies and literacy in handling digital technology has not kept pace, resulting in a significant disparity among individuals. Existing measurements of digital literacy were developed before widespread information and communications technology device adoption, mainly focusing on one's perceptions of their proficiency and the utility of device operation.
View Article and Find Full Text PDFACS Nano
January 2025
NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisbon 1169-056, Portugal.
The "" under this Perspective underline the importance of interdisciplinary collaboration and partnerships across several disciplines, such as medical science and technology, medicine, bioengineering, and computational approaches, in bridging the gap between research, manufacturing, and clinical applications. Effective communication is key to bridging team gaps, enhancing trust, and resolving conflicts, thereby fostering teamwork and individual growth toward shared goals. Drawing from the success of the COVID-19 vaccine development, we advocate the application of similar collaborative models in other complex health areas such as nanomedicine and biomedical engineering.
View Article and Find Full Text PDFJ Bras Nefrol
January 2025
Santa Casa de Porto Alegre, Porto Alegre, RS, Brazil.
Introduction: Acute kidney injury (AKI) in the setting of COVID-19 is associated with worse clinical and renal outcomes, with limited long-term data.
Aim: To evaluate critically ill COVID-19 patients with AKI that required nephrologist consultation (NC-AKI) in a tertiary hospital.
Methods: Prospective single-center cohort of critically ill COVID-19 adult patients with NC-AKI from May 1st, 2020, to April 30th, 2021.
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