Review
Biochemistry & Molecular Biology
Roberta Ettari, Santo Previti, Carla Di Chio, Maria Zappala
Summary: Malaria is a serious global public health issue, with chemotherapy being the only current treatment method due to lack of effective vaccine. However, the resistance to antimalarial drugs poses a challenge to the current therapeutic regimen. Therefore, the search for new drug targets is a pressing priority.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Carla Di Chio, Santo Previti, Giorgio Amendola, Rahul Ravichandran, Annika Wagner, Sandro Cosconati, Ute A. Hellmich, Tanja Schirmeister, Maria Zappala, Roberta Ettari
Summary: In this study, a new series of dipeptide nitriles were developed as reversible rhodesain inhibitors at a nanomolar level. These compounds were shown to directly bind to the active site of rhodesain and act as competitive inhibitors. The most promising compounds exhibited high binding affinity and good antiparasitic activity, making them potential lead compounds for the discovery of new drugs to treat Human African Trypanosomiasis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Subramanyam Vankadara, Yun Xuan Wong, Boping Liu, Yi Yang See, Li Hong Tan, Qian Wen Tan, Gang Wang, Ratna Karuna, Xue Guo, Shu Ting Tan, Jia Yi Fong, Joma Joy, C. S. Brian Chia
Summary: The COVID-19 pandemic has highlighted the urgent need for more antiviral drugs, with research focusing on peptidomimetic 3CLpro inhibitors as potential therapeutics. A head-to-head comparison of fifteen reported inhibitors in a standard assay was conducted to identify potent candidates for development, while also discussing inhibitor design and suitable warheads.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Hao Wang, Rongjuan Pei, Xin Li, Weilong Deng, Shuai Xing, Yanan Zhang, Chen Zhang, Shuai He, Hao Sun, Shuqi Xiao, Jin Xiong, Yecheng Zhang, Xinwen Chen, Yaxin Wang, Yu Guo, Bo Zhang, Luqing Shang
Summary: COVID-19 caused by SARS-CoV-2 has resulted in millions of infections and deaths worldwide. Researchers have identified the 3CL protease of SARS-CoV-2 as a potential target for developing drugs. They have successfully designed peptidomimetic inhibitors with excellent antiviral activity against SARS-CoV-2, indicating their potential as drug candidates.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Maude Giroud, Bernd Kuhn, Wolfgang Haap
Summary: This review article summarizes the drug discovery efforts in the research community from 2017 to 2022, focusing on the optimization of small molecule cysteine protease inhibitors and in vivo studies. Although potent and selective inhibitors for neglected tropical diseases have been identified, none of them have reached the stage of active clinical development.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Kanika Verma, Ayush Kumar Lahariya, Garima Verma, Monika Kumari, Divanshi Gupta, Neha Maurya, Anil Kumar Verma, Ashutosh Mani, Kristan Alexander Schneider, Praveen Kumar Bharti
Summary: The spread of antimalarial drug resistance is a significant challenge to global malaria elimination. Finding new therapeutic candidates is a priority in global health. In this study, a computational approach was used to screen approved drugs and identify potential FP2 inhibitors for the treatment of malaria. Several drugs were found to have good drug-likeness and binding affinity towards FP2, with two drugs showing similar biological activity to the known inhibitor E64. These findings can be used to design specific inhibitors or new antimalarial agents for malaria treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Wenhao Dai, Dirk Jochmans, Hang Xie, Hang Yang, Jian Li, Haixia Su, Di Chang, Jiang Wang, Jingjing Peng, Lili Zhu, Yong Nian, Rolf Hilgenfeld, Hualiang Jiang, Kaixian Chen, Leike Zhang, Yechun Xu, Johan Neyts, Hong Liu
Summary: A series of peptidomimetic aldehydes were designed and synthesized to target 3C(pro) of EV71 and SARS-CoV-2. Compound 18p showed potent antiviral and enzyme inhibitory activity, as well as good pharmacokinetic properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Fernanda R. Rocho, Vinicius Bonatto, Rafael F. Lameiro, Jeronimo Lameira, Andrei Leitao, Carlos A. Montanari
Summary: Cathepsin K (CatK) is a promising therapeutic target for diseases characterized by bone resorption, like osteoporosis. This review summarizes the patent literature on CatK inhibitors from 2011 to 2021 and their potential as new treatments for osteoporosis. The most explored inhibitors are nitrile-based inhibitors, and promising in vivo results have been disclosed. However, there is no approved drug targeting CatK yet.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2022)
Review
Virology
Varada Anirudhan, Hyun Lee, Han Cheng, Laura Cooper, Lijun Rong
Summary: The review provides information on potential treatment strategies for COVID-19 that target the essential proteins of the virus, specifically 3CL(pro) and PLpro, which are key in inhibiting viral replication and may offer insights from previous experience with SARS-CoV.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Luana Alves, Deborah A. Santos, Rodrigo Cendron, Fernanda R. Rocho, Thiago K. B. Matos, Andrei Leitao, Carlos A. Montanari
Summary: Peptidomimetics of dipeptidyl nitrile analog peptoids were synthesized as inhibitors of mammalian cysteine proteases of the papain superfamily. These nitrile-based peptoid analogs play a role in the secondary structure elements of peptides and proteins, making them resistant to proteolysis. The designed peptoids lose a hydrogen bond with cruzain Asp161, decreasing the affinity towards the enzyme.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Irina Stefanelli, Angela Corona, Carmen Cerchia, Emilia Cassese, Salvatore Improta, Elisa Costanzi, Sveva Pelliccia, Stefano Morasso, Francesca Esposito, Annalaura Paulis, Sante Scognamiglio, Francesco Saverio Di Leva, Paola Storici, Margherita Brindisi, Enzo Tramontano, Rolando Cannalire, Vincenzo Summa
Summary: Despite the availability of vaccines, monoclonal antibodies, and restrictions, there is a strong demand for new antiviral drugs that are both effective and safe against COVID-19. This study describes the design, synthesis, and biological activity of peptidomimetic covalent reversible inhibitors targeting the viral 3-chymotrypsin-like protease (3CLpro) which is essential for viral replication. These inhibitors showed potent activity against multiple coronaviruses, including SARS-CoV-2, MERS-CoV, and HCoV 229. The results suggest that these inhibitors have the potential to be developed as broad-spectrum antiviral drugs against future coronavirus pandemics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
S. Pant, G. Bhattacharya, N. R. Jena
Summary: This study investigates peptide inhibitors targeting the NS2B-NS3 protease of ZIKV and finds that the YKKR peptide inhibitor forms the most stable complex with the protease and strongly inhibits ZIKV proliferation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Pharmacology & Pharmacy
Abdur Rauf, Anees Ahmed Khalil, Ahmed Olatunde, Muneeb Khan, Sirajudheen Anwar, Ahmed Alafnan, Kannan R. R. Rengasamy
Summary: Marine habitats are rich in diverse life forms that offer potential sources of novel bioactive compounds, including protease inhibitors with significant applications in pharmaceutical, nutraceutical, and cosmeceutical industries. Despite extensive research on protease inhibitors, many compounds have not advanced to clinical trials, highlighting the ongoing need for exploring new sources for their development.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Archi Sundar Paul, Rajib Islam, Md Rimon Parves, Abdulla Al Mamun, Imrul Shahriar, Md Imran Hossain, Md Nayeem Hossain, Md Ackas Ali, Mohammad A. Halim
Summary: This study highlights the importance of the main protease (Mpro) of SARS-CoV-2 in viral replication and transcription, and suggests that targeting this protease can lead to the development of effective drugs. The researchers screened cysteine-focused ligands and identified candidates that strongly interacted with key residues of Mpro. Covalent docking and molecular dynamics simulation were performed to validate the interactions. The results showed that ligands containing acrylonitrile and amide warheads performed well and were predicted to be safer inhibitors. Overall, this study provides valuable insights for designing an effective drug for COVID-19 treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Mengwei Zhu, Tiantian Fu, Mengyuan You, Junyuan Cao, Hanxi Yang, Xinyao Chen, Qiumeng Zhang, Yechun Xu, Xiangrui Jiang, Leike Zhang, Haixia Su, Yan Zhang, Jingshan Shen
Summary: A series of new peptidomimetic SARS-CoV-2 3CL protease inhibitors with unique P2 and P4 positions were synthesized and evaluated. Compound 1a and 2b exhibited significant 3CLpro inhibitory activities with IC50 values of 18.06 nM and 22.42 nM, respectively. Both 1a and 2b showed excellent in vitro antiviral activities against SARS-CoV-2, with EC50 values of 313.0 nM and 170.2 nM, respectively, which were 2- and 4-fold better than nirmatrelvir. Furthermore, these compounds demonstrated no significant cytotoxicity in vitro. Metabolic stability tests and pharmacokinetic studies revealed improved metabolic stability of 1a and 2b in liver microsomes, and 2b showed similar pharmacokinetic parameters to nirmatrelvir in mice.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Tanja Schirmeister, Jochen Kesselring, Sascha Jung, Thomas H. Schneider, Anastasia Weickert, Johannes Becker, Wook Lee, Denise Bamberger, Peter R. Wich, Ute Distler, Stefan Tenzer, Patrick Johe, Ute A. Hellmich, Bernd Engels
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2016)
Article
Chemistry, Medicinal
Antonio Latorre, Tanja Schirmeister, Jochen Kesselring, Sascha Jung, Patrick Johe, Ute A. Hellmich, Anna Heilos, Bernd Engels, R. Luise Krauth-Siegel, Natalie Dirdjaja, Liedo Bou-Iserte, Santiago Rodriguez, Florenci V. Gonzalez
ACS MEDICINAL CHEMISTRY LETTERS
(2016)
Article
Chemistry, Multidisciplinary
A. Scala, N. Micale, A. Piperno, A. Rescifina, T. Schirmeister, J. Kesselring, G. Grassi
Article
Chemistry, Medicinal
Bernd Kuhn, Michal Tichy, Lingle Wang, Shaughnessy Robinson, Rainer E. Martin, Andreas Kuglstatter, Jorg Benz, Maude Giroud, Tanja Schirmeister, Robert Abel, Francois Diederich, Jerome Hert
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Chemistry, Organic
Ming W. Shi, Scott G. Stewart, Alexandre N. Sobolev, Birger Dittrich, Tanja Schirmeister, Peter Luger, Malte Hesse, Yu-Sheng Chen, Peter R. Spackman, Mark A. Spackman, Simon Grabowsky
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Tanja Schirmeister, Swarna Oli, Hongmei Wu, Gerardo Della Sala, Valeria Costantino, Ean-Jeong Seo, Thomas Efferth
Article
Biochemistry & Molecular Biology
Santiago Royo, Tanja Schirmeister, Marcel Kaiser, Sascha Jung, Santiago Rodriguez, Jose Manuel Bautista, Florenci V. Gonzalez
BIOORGANIC & MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Philipp Fey, Roula Chartomatsidou, Werner Kiefer, Jeremy C. Mottram, Christian Kersten, Tanja Schirmeister
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Philipp Klein, Patrick Johe, Annika Wagner, Sascha Jung, Jonas Kuehlborn, Fabian Barthels, Stefan Tenzer, Ute Distler, Waldemar Waigel, Bernd Engels, Ute A. Hellmich, Till Opatz, Tanja Schirmeister
Article
Biochemistry & Molecular Biology
Philipp Klein, Fabian Barthels, Patrick Johe, Annika Wagner, Stefan Tenzer, Ute Distler, Thien Anh Le, Paul Schmid, Volker Engel, Bernd Engels, Ute A. Hellmich, Till Opatz, Tanja Schirmeister
Article
Biochemistry & Molecular Biology
Hannah Maus, Fabian Barthels, Stefan Josef Hammerschmidt, Katja Kopp, Benedikt Millies, Andrea Gellert, Alessia Ruggieri, Tanja Schirmeister
Summary: In recent years, dengue virus (DENV) and Zika virus (ZIKV) have emerged as global health issues due to climate change and increasing globalization. New allosteric inhibitors have been developed with improved efficacy and selectivity against the two viruses, showing promising potential for antiviral therapy.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ines Schmidt, Sarah Goellner, Antje Fuss, August Stich, Anna Kucharski, Tanja Schirmeister, Elena Katzowitsch, Heike Bruhn, Alexandra Miliu, R. Luise Krauth-Siegel, Ulrike Holzgrabe
BIOORGANIC & MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Lara Massai, Luigi Messori, Nicola Micale, Tanja Schirmeister, Louis Maes, Dolores Fregona, Maria Agostina Cinellu, Chiara Gabbiani
Article
Chemistry, Medicinal
Tanja Schirmeister, Janina Schmitz, Sascha Jung, Torsten Schmenger, R. Luise Krauth-Siegel, Michael Guetschow
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Medicinal
Maude Giroud, Jakov Ivkovic, Mara Martignoni, Marianne Fleuti, Nils Trapp, Wolfgang Haap, Andreas Kuglstatter, Jorg Benz, Bernd Kuhn, Tanja Schirmeister, Francois Diederich