The castor plant (Ricinus communis) is primarily known for its seeds, which contain a unique fatty acid called ricinoleic acid with several industrial and commercial applications. Castor seeds also contain ricin, a toxin considered a chemical and biological warfare agent. Despite years of investigation, there is still no effective antidote or vaccine available. However, some progress has been made, and the development of an effective treatment may be on the horizon. To provide an updated overview of this issue, we have conducted a comprehensive review of the literature on the current state of research in the fight against ricin. This review is based on the reported research and aims to address the challenges faced by researchers, as well as highlight the most successful cases achieved thus far. Our goal is to encourage the scientific community to continue their efforts in this critical search.

• Keywords
• Ricin inhibitors, chemical warfare, drug design, medicinal chemistry, ribosome-inactivating protein., ricin A chain,
• MeSH
• Antidotes * chemistry   pharmacology   MeSH
• Chemical Warfare Agents chemistry   MeSH
• Humans MeSH
• Ricin * antagonists & inhibitors   chemistry   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antidotes * MeSH
• Chemical Warfare Agents MeSH
• Ricin * MeSH

Açaí, Euterpe oleracea Mart., is a native plant from the Amazonian and is rich in several phytochemicals with anti-tumor activities. The aim was to analyze the effects of açaí seed oil on colorectal adenocarcinoma (ADC) cells. In vitro analyses were performed on CACO-2, HCT-116, and HT-29 cell lines. The strains were treated with açaí seed oil for 24, 48, and 72 h, and cell viability, death, and morphology were analyzed. Molecular docking was performed to evaluate the interaction between the major compounds in açaí seed oil and Annexin A2. The viability assay showed the cytotoxic effect of the oil in colorectal adenocarcinoma cells. Acai seed oil induced increased apoptosis in CACO-2 and HCT-116 cells and interfered with the cell cycle. Western blotting showed an increased expression of LC3-B, suggestive of autophagy, and Annexin A2, an apoptosis regulatory protein. Molecular docking confirmed the interaction of major fatty acids with Annexin A2, suggesting a role of açaí seed oil in modulating Annexin A2 expression in these cancer cell lines. Our results suggest the anti-tumor potential of açaí seed oil in colorectal adenocarcinoma cells and contribute to the development of an active drug from a known natural product.

• Keywords
• Annexin A2, Euterpe oleracea Mart., apoptosis, autophagy, polyphenols,
• Publication type
• Journal Article MeSH

In response to the COVID-19 pandemic, and the lack of effective and safe antivirals against it, we adopted a new approach in which food supplements with vital antiviral characteristics, low toxicity, and fast excretion have been targeted. The structures and chemical properties of the food supplements were compared to the promising antivirals against SARS-COV-2. Our goal was to exploit the food supplements to mimic the topical antivirals' functions but circumventing their severe side effects, which has limited the necessary dosage needed to exhibit the desired antiviral activity. On this line, after a comparative structural analysis of the chemicals mentioned above, and investigation of their potential mechanisms of action, we selected caffeine and some compounds of the vitamin B family and further applied molecular modeling techniques to evaluate their interactions with the RDB domain of the Spike protein of SARS-CoV-2 (SC2Spike) and its corresponding binding site on human ACE-2 (HssACE2). Our results pointed to vitamins B1 and B6 in the neutral form as potential binders to the HssACE2 RDB binding pocket that might be able to impair the SARS-CoV-2 mechanism of cell invasion, qualifying as potential leads for experimental investigation against COVID-19.

• Keywords
• COVID-19, Caffeine, Docking, Molecular dynamic simulations, Vitamin B,
• MeSH
• Antiviral Agents pharmacology   chemistry   MeSH
• COVID-19 Drug Treatment * MeSH
• Caffeine pharmacology   MeSH
• Humans MeSH
• Niacinamide MeSH
• Pandemics MeSH
• Pyridoxamine MeSH
• Drug Design MeSH
• SARS-CoV-2 MeSH
• Molecular Docking Simulation MeSH
• Thiamine metabolism   MeSH
• Vitamins MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antiviral Agents MeSH
• Caffeine MeSH
• Niacinamide MeSH
• Pyridoxamine MeSH
• Thiamine MeSH
• Vitamins MeSH

Recently, we reported a library of 82 compounds, selected from different databanks through virtual screening and docking studies, and pointed to 6 among them as potential repurposed dual binders to both the catalytic site and the secondary binding pockets of subunit A of ricin (RTA). Here, we report additional molecular modeling studies of an extended list of compounds from the original library. Rounds of flexible docking followed by molecular dynamics simulations and further rounds of MM-PBSA calculations using a more robust protocol, enabled a better investigation of the interactions of these compounds inside RTA, the elucidation of their dynamical behaviors, and updating the list of the most important residues for the ligand binding. Four compounds were pointed as potential repurposed ricin inhibitors that are worth being experimentally investigated.

• Publication type
• Journal Article MeSH

The acute respiratory syndrome caused by the SARS-CoV-2, known as COVID-19, has been ruthlessly tormenting the world population for more than six months. However, so far no effective drug or vaccine against this plague have emerged yet, despite the huge effort in course by researchers and pharmaceutical companies worldwide. Willing to contribute with this fight to defeat COVID-19, we performed a virtual screening study on a library containing Food and Drug Administration (FDA) approved drugs, in a search for molecules capable of hitting three main molecular targets of SARS-CoV-2 currently available in the Protein Data Bank (PDB). Our results were refined with further molecular dynamics (MD) simulations and MM-PBSA calculations and pointed to 7 multi-target hits which we propose here for experimental evaluation and repurposing as potential drugs against COVID-19. Additional rounds of docking, MD simulations and MM-PBSA calculations with remdesivir suggested that this compound can also work as a multi-target drug against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

• Keywords
• SARS-CoV-2, drug repurposing, multi-target approach, virtual screening,
• MeSH
• Cysteine Endopeptidases MeSH
• COVID-19 Drug Treatment * MeSH
• Protease Inhibitors MeSH
• Coronavirus 3C Proteases MeSH
• Pharmaceutical Preparations MeSH
• Humans MeSH
• SARS-CoV-2 * MeSH
• Molecular Dynamics Simulation MeSH
• Molecular Docking Simulation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cysteine Endopeptidases MeSH
• Protease Inhibitors MeSH
• Coronavirus 3C Proteases MeSH
• Pharmaceutical Preparations MeSH