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The COVID-19 pandemic is ongoing and the benefit from vaccines is still insufficient since COVID-19 continues to be dia g-nosed in vaccinated individuals. It is, therefore, necessary to propose specific pharmacological treatments against COVID-19. A new therapeutic target on the human cellular membrane is AXL (anexelekto), proposed as an independent pathway by which interaction with the S protein of SARS-CoV-2 allows the virus to enter the cell, without the participation of ACE2. AXL serves as another gate through which SARS-CoV-2 can enter cells. Therefore, any stage of COVID-19 could be ameliorated by hindering the interaction between AXL and SARS-CoV-2. This study proposes ten compounds (1–10), selected by mole-cu lar docking and using a library of nearly 500,000 compounds, to develop a new drug that will decrease the interaction of AXL with the S protein of SARS-CoV-2. These compounds have a specific potential site of interaction with AXL, between Glu59, His61, Glu70 and Ser74 amino acids. This site is necessary for the interaction of AXL with the S protein. With this, we propose to develop a new adjuvant treatment against COVID-19.

Trichomoniasis is a public health problem worldwide. Trichomoniasis treatment consists of the use of nitroimidazole derivatives; however, therapeutic ineffectiveness occurs in 5 to 20 % of the cases. Therefore, it is essential to propose new pharmacological agents against this disease. In this work, esters of quinoxaline-7-carboxylate-1,4-di-N-oxide (EQX-NO) were evaluated in in vitro assays as novel trichomonicidal agents. Additionally, an in vitro enzyme assay and molecular docking analysis against triosephosphate isomerase of Trichomonas vaginalis to confirm their mechanism of action were performed. Ethyl (compound 12) and n-propyl (compound 37) esters of quinoxaline-7-carboxy-late-1,4-di-N-oxide derivatives showed trichomonicidal activity comparable to nitazoxanide, whereas five methyl (compounds 5, 15, 19, 20 and 22), four isopropyl (compounds 28, 29, 30 and 34), three ethyl (compounds 4, 13 and 23) and one npropyl (compound 35) ester derivatives displayed activity comparable to albendazole. Compounds 6 and 20 decreased 100 % of the enzyme activity of recombinant protein triosephosphate isomerase.

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Background: Alzheimer´s disease (AD) is one of the most common forms of dementia, is characterized by memory loss and cognitive impairment that affects more than 30 million people worldwide. The pathogenesis of Alzheimer's disease is primary driven by brain accumulation of the amyloid β peptide generated from the amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. In this study, we propose an approach by molecular docking to select compounds as γ-secretase inhibitors for decreasing the APP generation., Methods: We selected potential γ-secretase inhibitors by molecular docking in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in presenilin-1 (PS-1), using a chemical library of over 500,000 compounds., Results: Eight compounds (AZ1 - AZ8) were selected by molecular docking to develop γ-secretase inhibitors for decreasing the APP generation., Conclusions: AZ1 - AZ8 compounds could be interacting in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in PS-1. These compounds could specifically interact in the binding pocket in PS-1 to prevent/decrease the APP generation, to develop a new drug against Alzheimer's disease., Competing Interests: The authors declare no conflicts of interest.

Background: : Cancer continues worldwide. It has been reported that OTUB1, a cysteine protease, plays a critical role in a variety of tumors and is strongly related to tumor proliferation, migration, and clinical prognosis by its functions on deubiquitination. Drug advances continue against new therapeutic targets. In this study we used OTUB1 to develop a specific pharmacological treatment to regulate deubiquitination by OTUB1. The aim of this research is to regulate OTUB1 functions., Methods: By molecular docking in a specific potential OTUB1 interaction site between Asp88, Cys91, and His26 amino acids, using a chemical library of over 500,000 compounds, we selected potential inhibitors of the OTUB1 catalytic site., Results: Ten compounds (OT1 - OT10) were selected by molecular docking to develop a new anti-cancer drug to decrease OTUB1 functions in cancer processes., Conclusion: OT1 - OT10 compounds could be interacting in the potential site between Asp88, Cys91, and His265 amino acids in OTUB1. This site is necessary for the deubiquitinating function of OTUB1. Therefore, this study shows another way to attack cancer., Competing Interests: The authors declare no conflict of interest.