VLP-Based Vaccines as a Suitable Technology to Target Trypanosomatid Diseases

Research on vaccines against trypanosomatids, a family of protozoa that cause neglected tropical diseases, such as Chagas disease, leishmaniasis, and sleeping sickness, is a current need. Today, according to modern vaccinology, virus-like particle (VLP) technology is involved in many vaccines, including those undergoing studies related to COVID-19. The potential use of VLPs as vaccine adjuvants opens an opportunity for the use of protozoan antigens for the development of vaccines against diseases caused by Trypanosoma cruzi, Leishmania spp., and Trypanosoma brucei. In this context, it is important to consider the evasion mechanisms of these protozoa in the host and the antigens involved in the mechanisms of the parasite–host interaction. Thus, the immunostimulatory properties of VLPs can be part of an important strategy for the development and evaluation of new vaccines. This work aims to highlight the potential of VLPs as vaccine adjuvants for the development of immunity in complex diseases, specifically in the context of tropical diseases caused by trypanosomatids.

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Quinoline-based Compounds as Key Candidates to Tackle Drug Discovery Programs of Microbicidal Agents

Current Pharmaceutical Design ◽

10.2174/1381612826666201006125644 ◽

2020 ◽

Vol 26 ◽

Author(s):

Aline Nefertiti Silva da Gama ◽

Maria de Nazaré Correia Soeiro

Keyword(s):

Drug Discovery ◽

Trypanosoma Brucei ◽

Anticancer Agents ◽

Biological Effect ◽

Heterocyclic Compounds ◽

Neglected Tropical Diseases ◽

Pharmacological Properties ◽

Tropical Diseases ◽

Clinical Use ◽

Leishmania Spp

: Quinolines are nitrogen heterocyclic compounds ubiquitous in nature and largely used as a structural component of dyes, solvent for resins, terpenes as well as during the production of several other chemical stuffs, including pesticides. Quinolines, such as quinine and chloroquine, exhibit various pharmacological properties, acting as antimalarial drugs, antiparasitic, antibacterial, antiviral, antifungal, and anticancer agents, besides being in clinical use for autoimmune diseases. Presently, a brief review is present regarding the biological effect and clinical use of quinolines and derivatives upon two trypanosomatids agents of important neglected tropical diseases; Trypanosoma cruzi, Trypanosoma brucei spp and Leishmania spp, which trigger Chagas disease, sleeping sickness and leishmaniasis, respectively, also extending to a glance update of their potential application towards other microbes relevant for emerging illness caused by fungi, bacteria and virus, including the pandemic Covid-19.

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Immunizations and vaccines: a decade of successes and reversals, and a call for ‘vaccine diplomacy’

International Health ◽

10.1093/inthealth/ihz024 ◽

2019 ◽

Vol 11 (5) ◽

pp. 331-333 ◽

Cited By ~ 4

Author(s):

Peter J Hotez

Keyword(s):

Respiratory Virus ◽

Neglected Tropical Diseases ◽

Tropical Diseases ◽

Virus Infections ◽

Vaccination Programs ◽

Vaccine Preventable Diseases ◽

Health Gains ◽

Potential Development ◽

Respiratory Virus Infections ◽

New Vaccines

Abstract Over the last decade we have seen extraordinary public health gains due to expansions in global vaccination programs led by United Nations (UN) agencies, including Gavi, the Vaccine Alliance, UNICEF and the WHO. These initiatives have reduced childhood deaths from measles, tetanus and other vaccine-preventable diseases by almost one half. There is additional excitement over the potential development and introduction of new vaccines to prevent highly lethal respiratory virus infections, as well as tuberculosis, malaria, HIV/AIDS and several neglected tropical diseases. However, these successes are under threat due to political instability, conflict and an accelerating antivaccine movement. New initiatives in vaccine diplomacy will be required to combat these challenges.

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The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides in the Fight against Neglected Tropical Diseases

Molecules ◽

10.3390/molecules200815392 ◽

2015 ◽

Vol 20 (8) ◽

pp. 15392-15433 ◽

Cited By ~ 24

Author(s):

Angélique Lewies ◽

Johannes Wentzel ◽

Garmi Jacobs ◽

Lissinda Du Plessis

Keyword(s):

Antimicrobial Peptides ◽

Neglected Tropical Diseases ◽

Tropical Diseases ◽

Structural Analogues ◽

Potential Use

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Defeating the trypanosomatid trio: proteomics of the protozoan parasites causing neglected tropical diseases

RSC Medicinal Chemistry ◽

10.1039/d0md00122h ◽

2020 ◽

Vol 11 (6) ◽

pp. 625-645 ◽

Cited By ~ 1

Author(s):

Anutthaman Parthasarathy ◽

Karunakaran Kalesh

Keyword(s):

Trypanosoma Cruzi ◽

Trypanosoma Brucei ◽

Neglected Tropical Diseases ◽

Tropical Diseases ◽

Protozoan Parasites ◽

Proteomic Techniques

This review highlights the key roles of proteomic techniques in the study of Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei parasites.

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Targeting pteridine reductase 1 and dihydrofolate reductase: the old is a new trend for leishmaniasis drug discovery

Future Medicinal Chemistry ◽

10.4155/fmc-2018-0512 ◽

2019 ◽

Vol 11 (16) ◽

pp. 2107-2130 ◽

Cited By ~ 6

Author(s):

Gustavo Machado das Neves ◽

Luciano P Kagami ◽

Itamar L Gonçalves ◽

Vera L Eifler-Lima

Keyword(s):

Dihydrofolate Reductase ◽

Drug Targets ◽

Neglected Tropical Diseases ◽

Molecular Targets ◽

New Drugs ◽

Tropical Diseases ◽

The World ◽

Leishmania Spp ◽

Systemic Manifestations ◽

Potential Drug Targets

Leishmaniasis is one of the major neglected tropical diseases in the world and it is considered endemic in 88 countries. This disease is transmitted by a Leishmania spp. infected sandfly and it may lead to cutaneous or systemic manifestations. The preconized treatment has low efficacy and there are cases of resistance to some drugs. Therefore, the search for new efficient molecular targets that can lead to the preparation of new drugs must be pursued. This review aims to evaluate both Leishmania enzymes PTR1 and DHFR-TS as potential drug targets, highlight their inhibitors and to discuss critically the use of chemoinformatics to elucidate interactions and propose new molecules against these enzymes.

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Preventing the next pandemic and tackling antiscience: an interview with Peter Hotez

Future Microbiology ◽

10.2217/fmb-2021-0088 ◽

2021 ◽

Author(s):

Peter Hotez

Keyword(s):

Product Development ◽

Vaccine Development ◽

Neglected Tropical Diseases ◽

Tropical Diseases ◽

Baylor College ◽

Hookworm Infection ◽

Molecular Virology ◽

National School ◽

Physician Scientist ◽

New Vaccines

This interview was conducted by Atiya Henry, Commissioning Editor of Future Microbiology. Peter J Hotez, MD, PhD is Dean of the National School of Tropical Medicine and Professor of Pediatrics and Molecular Virology & Microbiology at Baylor College of Medicine. He is an internationally-recognized physician-scientist in neglected tropical diseases and vaccine development. As head of the Texas Children’s Center for Vaccine Development, he leads a team and product development partnership for developing new vaccines for hookworm infection, schistosomiasis, leishmaniasis, Chagas disease and SARS/MERS/SARS-2 coronavirus. Dr Hotez has authored more than 500 original papers and is the author of four single-author books. Most recently as both a vaccine scientist and autism parent, he has led national efforts to defend vaccines and to serve as an ardent champion of vaccines going up against a growing national ‘antivax’ threat.

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The use of Sulfonamide Derivatives in the Treatment of Trypanosomatid Parasites including Trypanosoma cruzi, Trypanosoma brucei, and Leishmania ssp

Medicinal Chemistry ◽

10.2174/1573406415666190620141109 ◽

2020 ◽

Vol 16 (1) ◽

pp. 24-38 ◽

Cited By ~ 1

Author(s):

Cauê B. Scarim ◽

Rafael C. Chelucci ◽

Jean L. dos Santos ◽

Chung M. Chin

Keyword(s):

Trypanosoma Cruzi ◽

Trypanosoma Brucei ◽

Human African Trypanosomiasis ◽

Neglected Tropical Diseases ◽

Economic Incentive ◽

Tropical Diseases ◽

Lipinski’S Rule ◽

Novel Drugs ◽

Trypanosomatid Parasites ◽

Research And Policy

More than 10 million people around the world are afflicted by Neglected Tropical Diseases, such as Chagas Disease, Human African Trypanosomiasis, and Leishmania. These diseases mostly occur in undeveloped countries that suffer from a lack of economic incentive, research, and policy for new compound development. Sulfonamide moieties are effective scaffolds present in several compounds that are determinants to treat various diseases, principally neglected tropical diseases. This review article examines the contribution of these scaffolds in medicinal chemistry in the last five years, focusing on three trypanosomatid parasites: Trypanosoma cruzi, Trypanosoma brucei, and Leishmania ssp. We also present perspectives for their use in drug designs in an effort to contribute to new drug development. In addition, we consider the physicochemical parameters, whose molecules all presented according to Lipinski's rule. The correlation between the selective index and LogP was evaluated, showing that sulfonamide derivatives can act differently against each trypanosomatid parasite. Moreover, the approaches of novel drugs and technologies are very important for the eventual drug discovery against trypanosomatid diseases.

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