Krasimir A. Spasov
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View article: Proof-of-concept studies with a computationally designed M<sup>pro</sup>inhibitor as a synergistic combination regimen alternative to Paxlovid
Proof-of-concept studies with a computationally designed M<sup>pro</sup>inhibitor as a synergistic combination regimen alternative to Paxlovid Open
As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-Co…
View article: Prodrug nanotherapy demonstrates <i>in vivo</i> anticryptosporidial efficacy in a mouse model of chronic <i>Cryptosporidium</i> infection
Prodrug nanotherapy demonstrates <i>in vivo</i> anticryptosporidial efficacy in a mouse model of chronic <i>Cryptosporidium</i> infection Open
Enteric-coated oral nanotherapy shows in vivo anticryptosporidial efficacy.
View article: Exploring novel <scp>HIV</scp>‐1 reverse transcriptase inhibitors with drug‐resistant mutants: A double mutant surprise
Exploring novel <span>HIV</span>‐1 reverse transcriptase inhibitors with drug‐resistant mutants: A double mutant surprise Open
HIV‐1 reverse transcriptase (RT) remains a key target for HIV drug development. As successful management of the disease requires lifelong treatment, the emergence of resistance mutations is inevitable, making development of new RT inhibito…
View article: Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase
Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase Open
Reverse transcriptase (RT) from the human immunodeficiency virus continues to be an attractive drug target for antiretroviral therapy. June 2022 will commemorate the 30th anniversary of the first Human Immunodeficiency Virus (HIV) RT cryst…
View article: Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency
Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency Open
Non-covalent inhibitors of the main protease (Mpro) of SARS-CoV-2 having a pyridinone core were previously reported with IC50 values as low as 0.018 μM for inhibition of enzymatic activity and EC50 values as low as 0.8 μM for inhibition of…
View article: Long‐acting and extended‐release implant and nanoformulations with a synergistic antiretroviral two‐drug combination controls <scp>HIV</scp>‐1 infection in a humanized mouse model
Long‐acting and extended‐release implant and nanoformulations with a synergistic antiretroviral two‐drug combination controls <span>HIV</span>‐1 infection in a humanized mouse model Open
The HIV pandemic has affected over 38 million people worldwide with close to 26 million currently accessing antiretroviral therapy (ART). A major challenge in the long‐term treatment of HIV‐1 infection is nonadherence to ART. Long‐acting a…
View article: Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations
Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations Open
Starting from our previous finding of 14 known drugs as inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19, we have redesigned the weak hit perampanel to yield multiple noncovalent, nonpeptidic inhibit…
View article: Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead
Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead Open
Covalent inhibitors of wild-type HIV-1 reverse transcriptase (CRTIs) are reported. Three compounds derived from catechol diether non-nucleoside inhibitors (NNRTIs) with addition of a fluorosulfate warhead are demonstrated to covalently mod…
View article: Structural investigation of <scp>2‐naphthyl</scp> phenyl ether inhibitors bound to <scp>WT</scp> and <scp>Y181C</scp> reverse transcriptase highlights key features of the <scp>NNRTI</scp> binding site
Structural investigation of <span>2‐naphthyl</span> phenyl ether inhibitors bound to <span>WT</span> and <span>Y181C</span> reverse transcriptase highlights key features of the <span>NNRTI</span> binding site Open
Human immunodeficiency virus (HIV)‐1 remains as a global health issue that is primarily treated with highly active antiretroviral therapy, a combination of drugs that target the viral life cycle. One class of these drugs are non‐nucleoside…
View article: Reply to Pandey et al.: Understanding the efficacy of a potential antiretroviral drug candidate in humanized mouse model of HIV infection
Reply to Pandey et al.: Understanding the efficacy of a potential antiretroviral drug candidate in humanized mouse model of HIV infection Open
We appreciate Pandey et al.’s (1) interest in further understanding our published work (2). Our responses are given below the excerpts from the Letter.Our first and foremost concern is the data presented in their figure 6C. We fail to unde…
View article: From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection
From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection Open
Significance Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of highly active antiretroviral therapy; however, concerns about poor pharmacological properties, dose restriction because of toxicity, and drug …
View article: Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography
Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography Open
Significance HIV-1 reverse transcriptase (RT) has been the prime target for anti-HIV chemotherapy; however, its rapid mutation often generates drug resistance. Prominent variant strains of HIV-1 that lead to treatment failure with nonnucle…
View article: Design, Conformation, and Crystallography of 2-Naphthyl Phenyl Ethers as Potent Anti-HIV Agents
Design, Conformation, and Crystallography of 2-Naphthyl Phenyl Ethers as Potent Anti-HIV Agents Open
Catechol diethers that incorporate a 7-cyano-2-naphthyl substituent are reported as non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Many of the compounds have 1-10 nM potencies toward wild-type HIV-1. An interesting conf…
View article: Potent Inhibitors Active against HIV Reverse Transcriptase with K101P, a Mutation Conferring Rilpivirine Resistance
Potent Inhibitors Active against HIV Reverse Transcriptase with K101P, a Mutation Conferring Rilpivirine Resistance Open
Catechol diether compounds have nanomolar antiviral and enzymatic activity against HIV with reverse transcriptase (RT) variants containing K101P, a mutation that confers high-level resistance to FDA-approved non-nucleoside inhibitors efavi…
View article: Structure-Based Evaluation of Non-nucleoside Inhibitors with Improved Potency and Solubility That Target HIV Reverse Transcriptase Variants
Structure-Based Evaluation of Non-nucleoside Inhibitors with Improved Potency and Solubility That Target HIV Reverse Transcriptase Variants Open
The development of novel non-nucleoside inhibitors (NNRTIs) with activity against variants of HIV reverse transcriptase (RT) is crucial for overcoming treatment failure. The NNRTIs bind in an allosteric pocket in RT ∼10 Å away from the act…