Review
Virology
Irene T. Weber, Yuan-Fang Wang, Robert W. Harrison
Summary: The HIV protease is a key target for antiviral therapy, but drug resistance poses a growing threat. Dr. Stephen Oroszlan's contributions to understanding the function of the HIV protease and the development of clinical inhibitors are highlighted. Drug-resistant protease variants serve as valuable models for studying resistance mechanisms and evolution.
Review
Pharmacology & Pharmacy
Matthew Weichseldorfer, Marvin Reitz, Olga S. Latinovic
Summary: Combined antiretroviral therapy (cART) is widely recommended for controlling HIV-1 replication and improving the quality of life of infected individuals. However, latent infected cells remain a major barrier to treatment efficacy in the long term.
Article
Biochemistry & Molecular Biology
Roberto Arrigoni, Luigi Santacroce, Andrea Ballini, Luigi Leonardo Palese
Summary: The availability of drugs capable of blocking microorganism replication is a major accomplishment in medicine, but the increasing number of resistant strains poses a significant challenge for infectious disease treatment. Therefore, the search for new potential ligands for pathogens' life cycle is a crucial research area today.
Article
Biochemistry & Molecular Biology
Sunday N. Okafor, Abigail Meyer, Jay Gadsden, Fadi Ahmed, Lilian Guzman, Hashim Ahmed, Jose A. Fernandez Romero, Pavimol Angsantikul
Summary: This study screened FDA-approved and investigational drugs for their potential as HIV-1 protease inhibitors. The findings revealed that CBR003PS and CBR013PS exhibited significant binding affinity to the HIV-1 protease with high stability, showing potential for repurposing as HIV-1 protease inhibitors.
Article
Plant Sciences
Chin-Soon Phan, Jakia Jerin Mehjabin, Andrea Roxanne J. Anas, Masahiro Hayasaka, Reiko Onoki, Juting Wang, Taiki Umezawa, Kenji Washio, Masaaki Morikawa, Tatsufumi Okino
Summary: Chemical investigation of the cyanobacterium Dolichospermum sp. NIES-1697 resulted in the discovery of two new compounds, nostosin G (1) and spiroidesin B (2), which were characterized and studied for their structure and biosynthesis.
JOURNAL OF NATURAL PRODUCTS
(2022)
Review
Biochemistry & Molecular Biology
Mohamed Amine Jmel, Hajer Aounallah, Chaima Bensaoud, Imen Mekki, Jindrich Chmelar, Fernanda Faria, Youmna M'ghirbi, Michalis Kotsyfakis
Summary: Protease inhibitors are regulatory proteins found in all kingdoms that play crucial roles in controlling proteases, with potential applications in human disease treatment and agriculture. PIs from tick salivary glands have unique pharmacological properties and are promising candidates for drug development, progressing to preclinical and clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Amiram Sananes, Itay Cohen, Irit Allon, Oshrit Ben-David, Raghda Abu Shareb, Ksenia M. Yegodayev, David Stepensky, Moshe Elkabets, Niv Papo
Summary: Targeted therapies for prostate, breast, and ovarian cancers are based on their activity against primary tumors rather than their anti-metastatic activity. There is an urgent need for new agents targeting the metastatic process. Mesotrypsin and KLK6 are attractive putative targets for therapeutic intervention.
MOLECULAR ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
V. Marcel Alavi
Summary: The OMA1 protease in the mitochondrial inner membrane has potential as a drug target for complex diseases in the elderly. Its activation is related to cellular stress and apoptosis, and its inhibition can delay or prevent apoptosis in animal models. Understanding OMA1's structure and regulation is still limited, and technical challenges in OMA1 drug screens need to be addressed. Potent OMA1 inhibitors hold promise as a new class of cytoprotective medicines for disorders influenced by dysfunctional mitochondria.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Infectious Diseases
Leonardo Calza, Isabella Bon, Marina Tadolini, Marco Borderi, Vincenzo Colangeli, Lorenzo Badia, Gabriella Verucchi, Giada Rossini, Caterina Vocale, Paolo Gaibani, Pierluigi Viale, Luciano Attard
Summary: The study reported a case series of 26 HIV-infected patients with COVID-19 diagnosed at S.Orsola Hospital in Italy. Among them, 19 were male, with a median age of 54 years, and 73% had one or more comorbidities. Only 5 patients with interstitial pneumonia were hospitalized, and there were no ICU admissions or deaths.
Article
Oncology
Soyeong Park, Andrew Auyeung, Denis L. Lee, Paul F. Lambert, Evie H. Carchman, Nathan M. Sherer
Summary: High-risk strains of human papillomavirus (HPV), such as HPV16, cause various cancers, including cervical cancer, which is a major cause of death for women globally. Anti-HPV vaccines are available but do not treat existing infections. Current treatments for HPV-associated cancers have side effects on healthy tissues, prompting the need for better targeted therapies. The study found that HIV protease inhibitors can selectively deplete HPV16 oncoproteins, suggesting their potential for treating HPV16-driven cancers.
Article
Biochemistry & Molecular Biology
Kolin M. Clark, Josh G. Kim, Qiankun Wang, Hongbo Gao, Rachel M. Presti, Liang Shan
Summary: The sensitization of the CARD8 inflammasome to non-nucleoside reverse transcriptase inhibitors (NNRTIs) can be achieved through chemical inhibition of the negative regulator DPP9. The DPP9 inhibitor Val-boroPro (VbP) can kill HIV-1-infected cells without NNRTIs and synergize with NNRTIs to promote clearance of infected cells. This offers a promising strategy for enhancing NNRTI efficacy in eliminating HIV-1 reservoirs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jessica Alves Nunes, Fabricia Nunes da Silva, Elany Barbosa da Silva, Clara Andrezza Crisostomo Bezerra Costa, Johnnatan Duarte de Freitas, Francisco Jaime Bezerra Mendonca-Junior, Miriam Aparecida Giardini, Jair Lage de Siqueira-Neto, James H. McKerrow, Thaiz Rodrigues Teixeira, Louis William Odeesho, Conor R. Caffrey, Silvia Helena Cardoso, Edeildo Ferreira da Silva-Junior
Summary: A virtual fragment-based drug design approach was used to develop coumarin-based analogs that can inhibit two cysteine proteases of Trypanosoma cruzi and T. brucei. One compound, FN-27, showed inhibitory activity against both CRZ and TbrCATL, as well as trypanocidal activity against T. cruzi-infected cells. Another compound, FN-10, exhibited activity against T. brucei trypomastigotes but did not inhibit CRZ or TbrCATL. Molecular dynamics simulations confirmed the binding modes of FN-27 with both proteases. These findings are valuable for the development of novel natural-product-based inhibitors targeting these cysteine proteases.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Veronna Marie, Michelle Gordon
Summary: This study used molecular dynamics simulations to explore the co-evolutionary molecular mechanisms of resistance in HIV-1 PR and Gag, showing that resistance mutations in PR can alter drug binding and exacerbate binding when mutant PRs are bound to mutated Gag cleavage sites. The research also demonstrated that co-selection of mutations in both enzyme and substrate can lead to complex mechanisms of resistance, affecting the active site and flap flexibility in PR.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Microbiology
Shobana Sundar, Shanmughavel Piramanayagam, Jeyakumar Natarajan
Summary: Proteases are enzymes that break amide bonds in polypeptides and proteins. They are involved in various human ailments, including cancers, skin infections, and urinary tract infections. Bacterial proteases play a significant role in disease progression, breaking down host defense proteins and contributing to pathogen virulence. In this study, we review different types of human disease-causing bacterial proteases and their potential inhibitors.
ARCHIVES OF MICROBIOLOGY
(2023)
Article
Virology
Janos Andras Motyan, Mario Miczi, Stephen Oroszlan, Jozsef Tozser
Summary: The study explored the sequence-dependent specificity of HIV-1 protease and provided insights into the potential role of NC processing in HIV-1 replication. Results showed the importance of alternative binding possibilities of substrates into HIV-1 PR, suggesting the significance of substrate modifications in studying viral mutagenesis and replication mechanisms.
Review
Biochemistry & Molecular Biology
Luciana Terra, Norman Ratcliffe, Helena Carla Castro, Ana Carolina Paulo Vicente, Paul Dyson
Summary: This review highlights the siderophore molecules produced by Streptomyces, showcasing their diverse chemical structures and bioactivities against pathogenic bacteria. Additionally, the possibility of using siderophores conjugated with antibiotics as an alternative to overcome bacterial resistance to drugs and improve therapeutic efficacy is discussed. Streptomyces is confirmed as an important source of siderophores, with potential as antibacterial agents.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Fisheries
C. A. C. Araujo, J. P. F. Pacheco, P. J. Waniek, R. B. Geraldo, A. Sibajev, A. L. Dos Santos, V. G. O. Evangelho, P. J. Dyson, P. Azambuja, N. A. Ratcliffe, H. C. Castro, C. B. Mello
Summary: The research describes a rhamnose-binding lectin (RBL) from Rhodnius prolixus, highlighting its potential importance in the immune response and gut microbiota homeostasis of the insect vector. Silencing of RpLec gene led to increased bacterial populations in the midgut of R. prolixus, indicating a role in regulating gut bacteria and immune defenses.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Review
Toxicology
Anne C. P. da Silva, Bianca A. M. C. Santos, Helena C. Castro, Carlos R. Rodrigues
Summary: This article reviews the toxicological effects of EHMC and BMDM on aquatic ecosystems and humans, highlighting their widespread presence in water samples and sediments globally. Strategies to reduce the harm caused by sunscreens include using natural photoprotectors like polyphenols or developing new, safer UV filters.
JOURNAL OF APPLIED TOXICOLOGY
(2022)
Review
Pharmacology & Pharmacy
Camila B. P. Da Costa, Ana Claudia De Menezes Cruz, Julio Cesar Q. Penha, Helena C. Castro, Luis E. R. Da Cunha, Norman A. Ratcliffe, Rafael Cisne, Francislene Juliana Martins
Summary: The search for an animal model that accurately reproduces the physiopathology of COVID-19 for testing new drugs is a challenge for researchers. Various animal models have been used, each with its own advantages and disadvantages, but further research is needed to determine the ideal model for drug development strategies in addition to vaccines.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Multidisciplinary
Paulo A. F. Pacheco, Daniel T. Gonzaga, Claudio C. Cirne-Santos, Caroline S. Barros, Max W. L. Gomes, Rafaela S. P. Gomes, Mariana C. Goncalves, Vitor F. Ferreira, Vitor W. Rabelo, Paula A. Abreu, Robson X. Faria, Gabriel O. de Resende, David R. da Rocha, Izabel C. N. P. Paixao, Fernando C. da Silva
Summary: Chikungunya virus is a re-emerging disease and there is an urgent need to develop new antiviral drugs. In this study, 19 derivatives were synthesized and evaluated, and 5 compounds showed potent activity. Compound 11a exhibited a high antiviral effect.
JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Dora C. S. Costa, Adriane S. Francisco, Beatriz V. A. Matuck, Priscila S. Furtado, Alana A. S. C. de Oliveira, Vitor W. -H. Rabelo, Plinio C. Sathler, Paula A. Abreu, Vitor F. Ferreira, Luiz Claudio R. P. da Silva, Fernando C. da Silva
Summary: A series of antitumoral prodrugs prototype of 1,2,3-triazoles-naphthoquinodoic acetyl derivatives were prepared by oxidative cycloaddition reaction and reductive acetylation, showing promising cytotoxic activity through inhibition of at least one topoisomerase II isoform.
JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY
(2022)
Editorial Material
Clinical Neurology
Victor Gustavo Oliveira Evangelho, Murilo Lamim Bello, Helena Carla Castro, Marcia Rodrigues Amorim
NEUROLOGICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Lais Cavalcanti dos Santos Velasco de Souza, Lucas Martins Alcantara, Pamella Antunes de Macedo-Sales, Nathalia Faria Reis, Debora Sena de Oliveira, Ricardo Luiz Dantas Machado, Reinaldo Barros Geraldo, Andre Luis Souza dos Santos, Vitor Francisco Ferreira, Daniel Tadeu Gomes Gonzaga, Fernando de Carvalho da Silva, Helena Carla Castro, Andrea Regina de Souza Baptista
Summary: This study identifies potential antifungal candidates for Sporothrix brasiliensis, a strain responsible for sporotrichosis in cats in the hyperendemic Brazilian region. Three hydrazone derivatives show promising antifungal activity against itraconazole-resistant S. brasiliensis, suggesting these synthetic compounds may be a valuable alternative treatment option.
Article
Biochemical Research Methods
Natalia L. von Ranke, Helena Carla Castro, Carlos R. Rodrigues
Summary: This study investigates the interactions between single-wall carbon nanotubes and three different anticancer drugs using computer modeling approaches. The results show that the physicochemical characteristics of the drugs influence their affinity towards the carbon nanotubes, and a diameter of 20.3 angstrom is found to be the most favorable for encapsulating the drugs.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Review
Toxicology
Natalia Lidmar von Ranke, Reinaldo Barros Geraldo, Andre Lima dos Santos, Victor G. O. Evangelho, Flaminia Flammini, Lucio Mendes Cabral, Helena Carla Castro, Carlos Rangel Rodrigues
Summary: This paper reviews the use of computational approaches for nanotoxicology prediction and discusses the characteristics of various computational methods used in nanomaterial analysis. It also describes the application of data integration methods in nanotoxicology.
COMPUTATIONAL TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bruna Costa Zorzanelli, Gabriel Ouverney, Fernanda P. Pauli, Anna Carolina Carvalho da Fonseca, Elan Cardozo Paes de Almeida, Danielle Goncalves de Carvalho, Patricia Abrao Possik, Vitor Won-Held Rabelo, Paula Alvarez Abreu, Bruno Pontes, Vitor Francisco Ferreira, Luana da Silva Magalhaes Forezi, Fernando de Carvalho da Silva, Bruno Kaufmann Robbs
Summary: Acridine-core naphthoquinone compounds were synthesized and evaluated for their antitumor activity in oral squamous cell carcinoma (OSCC) cells. Compound 4e showed high cytotoxicity and selectivity, as well as good tolerance in animals. Mechanistically, compound 4e promoted cell death by apoptosis and possibly targeted key enzymes involved in tumor progression.
Review
Toxicology
Camila Braz Pereira da Costa, Vanessa Ramos de Carvalho, Leide Lene Coelho Ferreira, Jorge Luiz Coelho Mattos, Leila de Mendonca Garcia, Marcia de Souza Antunes, Francislene Juliana Martins, Norman A. Ratcliffe, Rafael Cisne, Helena C. Castro
Summary: This study aims to optimize the production process of hyperimmune sera by analyzing previous research on enzymatic digestion of heterologous immunoglobulin G and protein fractionation with caprylic acid to determine the ideal conditions for these processes.
Article
Microbiology
Lais Cavalcanti dos Santos Velasco de Souza, Nathalia Faria Reis, Lucas Martins Alcantara, Simone Rocha Leal da Silveira Souto, Bruno de Araujo Penna, Renan Caetano Souza Santos, Bruno Kaufmann Robbs, Francisco Paiva Machado, Helena Carla Castro, Ricardo Luiz Dantas Machado, Leandro Rocha, Andrea Regina de Souza Baptista
Summary: This study aimed to evaluate the efficacy of different fractions of plant extracts against itraconazole-sensitive and low susceptibility Sporothrix brasiliensis isolates. Ethyl acetate extracts from Ocotea notata and Myrciaria floribunda exhibited the highest antimicrobial activities against sensitive S. brasiliensis. These extracts may serve as potential alternative therapies for this neglected zoonosis, but further research is needed.
BRAZILIAN JOURNAL OF MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Amanda A. Borges, Michele P. de Souza, Anna Carolina C. da Fonseca, Guilherme F. Wermelinger, Ruan C. B. Ribeiro, Adriane A. P. Amaral, Claudio Jose C. de Carvalho, Lucas S. Abreu, Lucas Nicolau de Queiroz, Elan C. P. de Almeida, Vitor W. Rabelo, Paula A. Abreu, Bruno Pontes, Vitor F. Ferreira, Fernando de C. da Silva, Luana da S. M. Forezi, Bruno K. Robbs
Summary: This study synthesized 16 chemoselectively derivated Mannich adducts of 1,4-naphthoquinones through a multiple component reaction. These new compounds exhibited good antitumor activity in oral squamous cell carcinoma models with higher selectivity and fewer side effects compared to other chemotherapy drugs. This finding provides important references and guidance for the development of new anticancer candidates.
Article
Infectious Diseases
Virginia Lucia Nazario Bonoldi, Natalino Hajime Yoshinari, Patricia Antonia Estima Abreu de Aniz, Rosa Maria Rodrigues Pereira
Summary: The study found that BB patients have increased levels of IL-8 and MIP-1 alpha/CCL3 (innate immunity) as well as MIP3B/CCL19 (Th1) and IL-17A (Th17) (adaptive immunity) compared to healthy controls. Levels of IL-1 beta, IL-8, and MIP-1 alpha/CCL3 were highest in acute BB patients, while TNF-alpha was associated with disseminated symptoms and humoral reactivity against Borrelia burgdorferi.
BRAZILIAN JOURNAL OF INFECTIOUS DISEASES
(2021)