Herbal plants, plant preparations and phytoconstituents have proved useful in attenuating infectious conditions and were the only remedies available, till the advent of antibiotics (many being of plant origin themselves). Among infectious diseases, viral diseases in particular, remain the leading cause of death in humans globally. A variety of phytoconstituents derived from medicinal herbs have been extensively studied for antiviral activity. Based on this rationale, an online search was performed, which helped to identify a large number of plant species harboring antiviral molecules. These herbal sources have been reported individually or in combinations across a large number of citations studied. Activities against rabies virus, Human immunodeficiency virus, Chandipura virus, Japanese Encephalitis Virus, Enterovirus, Influenza A/H1N1 and other influenza viruses were discovered during the literature search. This review includes all such plant species exhibiting antiviral properties. The review also encompasses composition and methodologies of preparing various antiviral formulations around the globe. An elaborate section on the formulations filed for patent registration, along with non-patented formulations, has also been included in this article. To conclude, herbal sources provide researchers enormous scope to explore and bring out viable alternatives against viral diseases, considering non-availability of suitable drug candidates and increasing resistance to existing drug molecules for many emerging and re-emerging viral diseases.

In this report, using NMR and molecular modeling, we have studied the structure of lysozyme-S100A6 complex and the influence of tranilast [N-(3, 4-dimethoxycinnamoyl) anthranilic acid], an antiallergic drug which binds to lysozyme, on lysozyme-S100A6 and S100A6-RAGE complex formation and, finally, on cell proliferation. We have found that tranilast may block the S100A6-lysozyme interaction and enhance binding of S100A6 to RAGE. Using WST1 assay, we have found that lysozyme, most probably by blocking the interaction between S100A6 and RAGE, inhibits cell proliferation while tranilast may reverse this effect by binding to lysozyme. In conclusion, studies presented in this work, describing the protein-protein/-drug interactions, are of great importance for designing new therapies to treat diseases associated with cell proliferation such as cancers.

About 50% of human cancers across the globe arise due to a mutation in the p53 gene which gives rise to its functional inactive form, and in the rest of the cancer the efficacy of active p53 (wild-type) is hindered by MDM2-mediated degradation. Breakdown of the p53-MDM2 association may constitute an effective strategy to stimulate or reinstate the activity of wild type p53, thereby reviving the p53 tumor suppressor capability. S100A1 has been revealed to associate with the N-terminal domain of MDM2 and p53 protein. We utilized NMR spectroscopy to study the interface amongst the S100A1 and N-terminal domain of MDM2. Additionally, the S100A1-MDM2 complex generated through the HADDOCK program was then superimposed with the p53 (peptide) -MDM2 complex reported earlier. The overlay indicated that a segment of S100A1 could block the interaction of p53 (peptide) -MDM2 complex significantly. To further justify our assumption, we performed HSQC-NMR titration for the S100A1 and p53 N-terminal domain (p53-TAD). The data obtained indicated that the S100A1 segment comprising nearly 17 residues have some common residues that interact with both MDM2 and p53-TAD. Further, we synthesized the 17-residue peptide derived from the S100A1 protein and attached it to the cell-penetrating HIV-TAT peptide. The HSQC-NMR competitive binding experiment revealed that Peptide 1 could successfully interfere with the p53-MDM2 interaction. Furthermore, functional effects of the peptide was validated in cancer cells. The results showed that Peptide 1 effectively inhibited cell proliferation, and increased the protein levels of p53 and its downstream p21 in MCF-7 cells. Treatment of Peptide 1 resulted in cell cycle arrest at G2/M phase, and also induced apoptotic cell death at higher concentration. Taken together, the results suggest that disruption of the interaction of p53 and MDM2 by Peptide 1 could activate normal p53 functions, leading to cell cycle arrest and apoptotic cell death in cancer cells. We proposed here that S100A1 could influence the p53-MDM2 interaction credibly and possibly reactivates the wild type p53 pathway.

S100P, a small calcium-binding protein, associates with the p53 protein with micromolar affinity. It has been hypothesized that the oncogenic function of S100P may involve binding-induced inactivation of p53. We used ¹H-¹⁵N HSQC experiments and molecular modeling to study the molecular interactions between S100P and p53 in the presence and absence of pentamidine. Our experimental analysis indicates that the S100P-53 complex formation is successfully disrupted by pentamidine, since S100P shares the same binding site for p53 and pentamidine. In addition, we showed that pentamidine treatment of ZR-75-1 breast cancer cells resulted in reduced proliferation and increased p53 and p21 protein levels, indicating that pentamidine is an effective antagonist that interferes with the S100P-p53 interaction, leading to re-activation of the p53-21 pathway and inhibition of cancer cell proliferation. Collectively, our findings suggest that blocking the association between S100P and p53 by pentamidine will prevent cancer progression and, therefore, provide a new avenue for cancer therapy by targeting the S100P-p53 interaction.

The Ca²⁺-sensing protein S100A11 of the S100 family is an important mediator of numerous biological functions and pathological conditions including cancer. The receptor for advanced glycation end products (RAGE) has been well accepted as the major receptor for several S100 family members. Here, we take the S100B protein as an antagonist to interfere with the interaction flanked by S100A11 and the RAGE V domain. We employed NMR spectroscopy to describe the interactions between the S100A11 and S100B proteins. ¹H–¹⁵N heteronuclear single-quantum correlation-NMR titrations showed the potential binding dynamics of S100A11 and S100B interactions. In the HADDOCK program, we constructed the S100A11–S100B heterodimer complex that was then superimposed with the S100A11–S100B complex structure in the same orientation as the S100A11–RAGE V domain complex. This overlay analysis showed that S100B could interfere in the binding section of S100A11 and the RAGE V domain. Additionally, water-soluble tetrazolium-1 assay provided a functional read-out of the effects of these proteins in an in vitro cancer model. Our study establishes that the development of an S100B antagonist could perform a vital part in the treatment of S100- and RAGE-dependent human diseases.