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Biology subjects

Reddy, P. M.

Publications and source records attributed to Reddy, P. M..

3 recordsLinked to original sources

High resolution cryo-EM structures of two potently SARS-CoV-2 neutralizing monoclonal antibodies of same donor origin that vary in neutralizing Omicron variants

While vaccines have by large been found to effective against the evolving SARS-CoV-2 variants, the profound and rapid effectivity of monoclonal antibodies (mAbs) in significantly reducing hospitalization to severe disease outcomes have also been demonstrated. In the present study, by high resolution cryo-electron microscopy (cryo-EM), we examined the structural insights of two trimeric spike (S) protein bound mAbs isolated from an Indian convalescent individual infected with ancestral SARS-CoV-2 which we recently reported to potently neutralize SARS-CoV-2 from its ancestral form through highly virulent Delta form however different in their ability to neutralize Omicron variants. Our findings showed binding and conformational heterogeneities of both the mAbs (THSC20.HVTR04 and THSC20.HVTR26) bound to S trimer in its apo and hACE-2 bound forms. Additionally, cryo-EM resolved structure assisted modeling highlighted key residues associated with the ability of these two mAbs to neutralize Omicron variants. Our findings highlighted key interacting features modulating antigen-antibody interacting that can further aid in structure guided antibody engineering to enhance their breadth and potency. HighlightsO_LITwo potent human mAbs obtained from a single donor differ binding to Omicron spikes C_LIO_LIPattern of binding and conformation of these mAbs bound to full length spike differs C_LIO_LIAntibody binding alters the conformational states of S trimer in its apo and hACE-2 bound forms. C_LIO_LICryo-EM structure guided modeling highlighted correlates of interacting residues associated with resistance and sensitivity of BA.1, BA.2, BA.4/BA.5 resistance and sensitivity against these mAbs. C_LI

biophysics↗

Host-induced silencing of the Colletotrichum gloeosporioides conidial morphology 1 gene (CgCOM1) confers resistance against Anthracnose disease in chilli and tomato

Anthracnose disease is caused by the ascomycetes fungal species Colletotrichum, which is responsible for heavy yield losses in chilli and tomato worldwide. Conventionally, harmful pesticides are used to contain anthracnose disease with limited success. In this study, we assessed the potential of Host-Induced Gene Silencing (HIGS) approach to target the Colletotrichum gloeosporioides COM1 (CgCOM1) developmental gene involved in the fungal conidial and appressorium formation, to restrict fungal infection in chilli and tomato fruits. For this study, we have developed stable transgenic lines of chilli and tomato expressing CgCOM1-RNAi construct employing Agrobacterium-mediated transformation. Transgenic plants were characterized by molecular and gene expression analyses. Production of specific CgCOM1 siRNA in transgenic chilli and tomato RNAi lines was confirmed by stem-loop RT-PCR. Fungal challenge assays on leaves and fruits showed that the transgenic lines were resistant to anthracnose disease-causing C. gloeosporioides in comparison to wild type and empty-vector control plants. RT-qPCR analyses in transgenic lines revealed barely any CgCOM1 transcripts in the C. gloeosporioides infected tissues, indicating near complete silencing of CgCOM1 gene expression in the pathogen. Microscopic examination of the Cg-challenged leaves of chilli-CgCOM1i lines revealed highly suppressed conidial germination, germ tube development, appressoria formation and mycelial growth of C. gloeosporioides, resulting in reduced infection of plant tissues. These results demonstrated highly efficient use of HIGS in silencing the expression of essential fungal developmental genes to inhibit the growth of pathogenic fungi, thus providing a highly precise approach to arrest the spread of disease.

plant biology↗

A novel bioactive molecule 5-β-Hydroxyltridecanyl benzoate identified in Pedalium Murex L. (Gokhru) fruit extracts showed antifungal activity against Sclerotinia sclerotiorum

Fruits of Pedalium murex known as, Gokhru is predominantly used in Ayurveda for its aphrodisiac properties and use in treatment of urological orders. However till now, bioactivity of this fruit has not been documented for plant protection against phytopathogenes, Hence in this regard, we investigated antimicrobial activity of P. murex fruit extracts (isolated from the different agro climatic zones of India) were tested against twelve microbial phytopathogens. From 29 fruit extracts, only 13 were found to be active against three pathogens viz. Botrytis cinerea, Rhizoctonia solani, and Sclerotinia sclerotiorum. Among the nine TLC fractions only one showed presence of a single peak, thus presence of a single compound in the crude extract. Based on lower IC50 value (328 g/ml) the crude fruit extract collected from Indore region was further characterized. Evaluation against screened phytopathogens indicates its activity. Further, structural characterization of this compound using FTIR and NMR revealed it to be a novel compound i.e. 5-{beta}-Hydroxyl tridecanyl benzoate. Our study paves a way to investigate effective dose of P. murex fruit extracts to utilize in plant protection programs. In future, a better method is required to scale up the process of bioactive molecule (5-{beta}-Hydroxyl tridecayl benzoate) extraction from P. murex or for its chemical synthesis.

microbiology↗