Biology subjects

Sidhu, S.

Publications and source records attributed to Sidhu, S..

3 recordsLinked to original sources

bioRxiv2020

Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations

Neutralizing antibodies (nAbs) hold promise as effective therapeutics against COVID-19. Here, we describe protein engineering and modular design principles that have led to the development of synthetic bivalent and tetravalent nAbs against SARS-CoV-2. The best nAb targets the host receptor binding site of the viral S-protein and its tetravalent versions can block entry with a potency that exceeds the bivalent nAbs by an order of magnitude. Structural studies show that both the bivalent and tetravalent nAbs can make multivalent interactions with a single S-protein trimer, observations consistent with the avidity and potency of these molecules. Significantly, we show that the tetravalent nAbs show much increased tolerance to potential virus escape mutants. Bivalent and tetravalent nAbs can be produced at large-scale and are as stable and specific as approved antibody drugs. Our results provide a general framework for developing potent antiviral therapies against COVID-19 and related viral threats, and our strategy can be readily applied to any antibody drug currently in development.

synthetic biology↗

bioRxiv2020

Using Citizen Science to build baseline data on tropical tree phenology

Large-scale and long-term understanding of the phenology of widespread tree species is lacking in the tropics, and particularly in the Indian subcontinent. In the absence of baseline information, the impacts of climate on tree phenology, and thus on trophic interactions downstream of tree phenology, are also poorly understood. Citizen scientists can help bridge this gap by contributing simple, technology-based information over large spatial scales and over the long term. In this study, we describe an India-wide citizen science initiative called SeasonWatch, with preliminary insights into contributor behaviour and species phenology. Over a period of 8 years, between 2011 and 2019, cumulative contributor numbers have increased every year, although consistent contribution remains constant and low. The phenological patterns in the 4 most-observed species (Jackfruit Artocarpus heterophyllus Lam., Mango Mangifera indica L., Tamarind Tamarindus indica L., and Indian Laburnum Cassia fistula L.) are described, with discernible seasonal peaks in flowering and fruiting. Seasonal peaks are influenced by tree phenology reported in the south Indian state of Kerala, which has the maximum number of contributors and most number of observations per contributor, comprising 89% of all observations. We look in detail at the flowering phenology of one particular species, Cassia fistula, which appears to show aberrant phenology, reflecting a potential shift away from historical baselines. Latitudinal patterns in the phenology of widespread species such as Mangifera indica are also discernible from 4 seasonal bioblitz events organised during 2018-19, with trees in lower latitudes exhibiting flowering and fruiting phenology earlier than the higher latitudes. We conclude that there are signs of shifts in phenological patterns, as in the case of C. fistula, and extend a call for action to sustain long-term interest and participation by contributors to develop a baseline for common tropical tree species that can be used to understand long-term consequences of climate change on tropical tree phenology.

ecology↗

bioRxiv2020

Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2.

Antibody-based interventions against SARS-CoV-2 could limit morbidity, mortality, and possibly disrupt epidemic transmission. An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, yet there is no consensus as to which assay should be used for such measurements. Using an infectious molecular clone of vesicular stomatitis virus (VSV) that expresses eGFP as a marker of infection, we replaced the glycoprotein gene (G) with the spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and developed a high-throughput imaging-based neutralization assay at biosafety level 2. We also developed a focus reduction neutralization test with a clinical isolate of SARS-CoV-2 at biosafety level 3. We compared the neutralizing activities of monoclonal and polyclonal antibody preparations, as well as ACE2-Fc soluble decoy protein in both assays and find an exceptionally high degree of concordance. The two assays will help define correlates of protection for antibody-based countermeasures including therapeutic antibodies, immune {gamma}-globulin or plasma preparations, and vaccines against SARS-CoV-2. Replication-competent VSV-eGFP-SARS-CoV-2 provides a rapid assay for testing inhibitors of SARS-CoV-2 mediated entry that can be performed in 7.5 hours under reduced biosafety containment.

microbiology↗