Chikungunya virus (CHIKV) is a mosquito-borne virus, which has created an alarming threat in the world due to unavailability of vaccine and antiviral compounds. The CHIKV nsP2 contains ATPase, RTPase, helicase and protease activities, whereas, nsP1 is a viral capping enzyme. In alphaviruses, the four non-structural proteins form the replication complex in the cytoplasm and this study characterizes the interaction between CHIKV nsP1 and nsP2. It was observed that, both the proteins co-localize in the cytoplasm and interact in the CHIKV infected cells by confocal microscopy and immunoprecipitation assay. Further, it was demonstrated through mutational analysis that, the amino acids 1-95 of nsP2 and 170-288 of nsP1 are responsible for their direct interaction. Additionally, it was noticed that, the ATPase activity of nsP2 is enhanced in the presence of nsP1, indicating the functional significance of this interaction. In silico analysis showed close (≤1.7 Å) polar interaction (hydrogen bond) between Glu4, Arg7, 96, 225 of nsP2 with Lys256, 206, Val367 and Phe312 of nsP1 respectively. Hence, this investigation provides molecular characterization of CHIKV nsP1-nsP2 interaction which might be a useful target for rational designing of antiviral drugs.
The SARS-CoV-2 infections in Indian people have been associated with a mucormycotic fungal infection caused by the filamentous fungi Rhizopus arrhizus. The sporangiospores of R. arrhizus are omnipresent in the environment and cause infection through inhalation or ingestion of contaminated air and foods. Therefore, the anti-sporangiospore activity of polyethyleneimine functionalized silver nanoparticles (PEI-f-Ag-NPs) with variable size and surface charge as a function of the molecular weight of PEI was explored. The results showed that both PEI-f-AgNP-1 and PEI-f-AgNP-2, potentially, attenuated the germination and reduced the viability of sporangiospores. Furthermore, the results showed that the minimum inhibitory concentration (MIC) values of both PEI-f-AgNP-1 and PEI-f-AgNP-2 (1.65 and 6.50 μg/mL, respectively) were dependent on the nanoparticle size and surface ζ potentials. Similarly, the sporangiospore germination inhibition at MIC values was recorded, showing 97.33% and 94% germination inhibition, respectively, by PEI-f-AgNP-1 and 2 within 24 h, respectively. The confocal laser scanning microscopy, SEM-EDS, and confocal Raman spectroscopy investigation of PEI-f-Ag-NPs treated sporangiospores confirmed size and surface charge-dependent killing dynamics in sporangiospores. To the best of our knowledge, this is the first investigation of the polyethyleneimine functionalized silver nanoparticle-mediated size and surface charge-dependent anti-sporangiospore activity against R. arrhizus, along with a possible antifungal mechanism.
21 November 2021 in Particle & Particle Systems Characterization
The COVID‐19 infections have posed an unprecedented global health emergency, with nearly three million deaths to date, and have caused substantial economic loss globally. Hence, an urgent exploration of effective and safe diagnostic/therapeutic approaches for minimizing the threat of this highly pathogenic coronavirus infection is needed. As an alternative to conventional diagnosis and antiviral agents, nanomaterials have a great potential to cope with the current or even future health emergency situation with a wide range of applications. Fundamentally, nanomaterials are physically and chemically tunable and can be employed for the next generation nanomaterial‐based detection of viral antigens and host antibodies in body fluids as antiviral agents, nanovaccine, suppressant of cytokine storm, nanocarrier for efficient delivery of antiviral drugs at infection site or inside the host cells, and can also be a significant tool for better understanding of the gut microbiome and SARS‐CoV‐2 interaction. The applicability of nanomaterial‐based therapeutic options to cope with the current and possible future pandemic is discussed here.