@article {49439,
	title = {Design of human ACE2 mimic miniprotein binders that interact with RBD of SARS-CoV-2 variants of concerns},
	journal = {Journal of Biomolecular Structure \& Dynamics},
	year = {2024},
	month = {JAN},
	type = {Article; Early Access},
	abstract = {<p>
	The world of medicine demands from the research community solutions to the emerging problem of SARS-CoV-2 variants and other such potential global pandemics. With advantages of specificity over small molecule drugs and designability over antibodies, miniprotein therapeutics offers a unique solution to the threats of rapidly emerging SARS-CoV-2 variants. Unfortunately, most of the promising miniprotein binders are de novo designed and it is not viable to generate molecules for each new variant. Therefore in this study, we demonstrate a method for design of miniprotein mimics from the interaction interphase of human angiotensin converting enzyme 2 (ACE2). ACE2 is the natural interacting partner for the SARS-CoV-2 spike receptor binding domain (RBD) and acts as a recognition molecule for viral entry into the host cells. Starting with ACE2 N-terminal triple helix interaction interphase, we generated more than 70 miniprotein sequences. Employing Rosetta folding and docking scores we selected 10 promising miniprotein candidates amongst which 3 were found to be soluble in lab studies. Further, using molecular mechanics (MM) calculations on molecular dynamics (MD) trajectories we test interaction of miniproteins with RBD from various variants of concern (VOC). Presently, we report two key findings; miniproteins in this study are generated using less than 10 lab testing experiments, yet when tested through in-vitro experiments, they show submicro to nanomolar affinities towards SARS-CoV-2 RBD. Also in simulation studies, when compared with previously developed therapeutics, our miniproteins display remarkable ability to mimic ACE2 interphase; making them an ideal solution to the ever evolving problem of VOCs.</p>
},
	keywords = {ACE2 mimics, miniprotein, protein design, SARS-CoV-2, therapeutics, Variant of concern},
	issn = {0739-1102},
	doi = {10.1080/07391102.2024.2310789},
	author = {Gaur, Neeraj K. and Khakerwala, Zeenat and Makde, Ravindra D.}
}
@article {49894,
	title = {Effectiveness of 3-amino-2-thiocyanato-α, β-unsaturated carbonyl compounds against chikungunya virus},
	journal = {Future Medicinal Chemistry},
	volume = {17},
	year = {2025},
	month = {JUN },
	pages = {1269-1279},
	type = {Article},
	abstract = {<p>Aim Chikungunya fever (CHIKF) caused by the chikungunya virus (CHIKV) is characterized by the presence of long-term polyarthralgia in a minor proportion of the infected patients. Currently, there are no FDA-approved antivirals available. This study evaluated the anti-CHIKV potential of 16 synthetic 3-amino-2-thiocyanato-alpha, beta-unsaturated carbonyl compounds and elucidated their probable mechanisms of action. Methods Anti-CHIKV activity of 16 compounds were investigated in Vero CCL-81 cells using focus forming unit assay (FFU). Dose-dependent and time-dependent antiviral assays were performed for the effective compounds. Molecular docking was performed to find out their interactions with viral proteins. Results Five compounds showed promising anti-CHIKV activity by reducing viral titer with \&gt;1 log10 FFU/ml. Dose-dependent studies revealed that the compound 3 g was more effective in reducing the virus titer with a half-maximal inhibitory concentration (IC50) of 0.4315 mu M and a selectivity index of 35.99. Docking analyses revealed that all the compounds mainly interact with the non-structural proteins of CHIKV. Conclusions These findings demonstrate the in vitro anti-CHIKV activity of these compounds, and their possible mode of action via interference with early stages of infection and replication processes. This study warrants further preclinical and clinical evaluation to establish their safety and efficacy as novel anti-CHIKV therapeutics.</p>
},
	keywords = {3-amino-2-thiocyanato-alpha, antivirals, beta-unsaturated carbonyl compounds, Chikungunya virus (CHIKV), nsP2 helicase, therapeutics},
	issn = {1756-8919},
	doi = {10.1080/17568919.2025.2517527},
	author = {Alagarasu, Kalichamy and Dhote, Radhika and Bagad, Pooja K. and Kharikar, Dwidhesh and Patil, Poonam and Roy, Diya and Shukla, Shridhar and Cherian, Sarah and Senthilkumar, Beeran and Parashar, Deepti}
}
