Understanding COVID-19 via comparative analysis of dark proteomes of SARS-CoV-2, human SARS and bat SARS-like coronaviruses.

The recently emerged coronavirus designated as SARS-CoV-2 (also known as 2019 novel coronavirus (2019-nCoV) or Wuhan coronavirus) is a causative agent of coronavirus disease 2019 (COVID-19), which is rapidly spreading throughout the world now. More than 1.21 million cases of SARS-CoV-2 infection and more than 67,000 COVID-19-associated mortalities have been reported worldwide till the writing of this article, and these numbers are increasing every passing hour. The World Health Organization (WHO) has declared the SARS-CoV-2 spread as a global public health emergency and admitted COVID-19 as a pandemic now. Multiple sequence alignment data correlated with the already published reports on SARS-CoV-2 evolution indicated that this virus is closely related to the bat severe acute respiratory syndrome-like coronavirus (bat SARS-like CoV) and the well-studied human SARS coronavirus (SARS-CoV). The disordered regions in viral proteins are associated with the viral infectivity and pathogenicity. Therefore, in this study, we have exploited a set of complementary computational approaches to examine the dark proteomes of SARS-CoV-2, bat SARS-like, and human SARS CoVs by analysing the prevalence of intrinsic disorder in their proteins. According to our findings, SARS-CoV-2 proteome contains very significant levels of structural order. In fact, except for nucleocapsid, Nsp8, and ORF6, the vast majority of SARS-CoV-2 proteins are mostly ordered proteins containing less intrinsically disordered protein regions (IDPRs). However, IDPRs found in SARS-CoV-2 proteins are functionally important. For example, cleavage sites in its replicase 1ab polyprotein are found to be highly disordered, and almost all SARS-CoV-2 proteins contains molecular recognition features (MoRFs), which are intrinsic disorder-based protein-protein interaction sites that are commonly utilized by proteins for interaction with specific partners. The results of our extensive investigation of the dark side of SARS-CoV-2 proteome will have important implications in understanding the structural and non-structural biology of SARS or SARS-like coronaviruses.

Optochemical control of Cu(I) homeostasis in mammalian cells.

Copper can act as a double-edged sword as it can cause fatal diseases when in excess or shortage. Precise control of copper homeostasis is maintained by a complex machinery inside cells. To overcome imbalances in copper concentration, we have developed a simple system to control the cellular copper concentration by using a photocaged chelator and light. This photocaged chelator allowed us to control cellular copper concentration in a spatiotemporal manner.

Repurposing pinacol esters of boronic acids for tuning viscoelastic properties of glucose-responsive polymer hydrogels: effects on insulin release kinetics.

In the era of the diabetes pandemic, injectable hydrogels (HGs) capable of releasing the desired amount of insulin under hyperglycemic conditions will significantly advance smart insulin development. Several smart boronic acid-based polymer HGs release insulin under high-glucose conditions. However, the correlation of insulin release characteristics with rheological properties is not well understood yet. Herein, we report a generalized and facile fabrication strategy of a new class of glucose-responsive hydrogels by crosslinking a biocompatible polymer, poly(vinyl alcohol) with pinacol esters of bisboronic acids via transesterification reactions. We show the versatility of the method by fabricating four hydrogels with diverse rheological properties. The HGs embody more than 70% water amenable for hosting insulin in the matrix. HG with high storage modulus, derived from 1,4-benzenediboronic acid bis(pinacol) ester releases ∼3 fold less insulin compared to softer HGs derived from acetylene-1,2-diyl bis(boronic acid pinacol ester) and bis[(pinacolato)boryl]methane under hyperglycemic conditions. We find that HG derived from the bis[(pinacolato)boryl]methane crosslinker exhibits superior insulin release properties due to the softness of the hydrogel matrix. We further show that the newly formulated gel is injectable without any structural change in the released insulin molecules and does not cause cytotoxicity. We believe that glucose-responsive hydrogels with tunable viscoelastic properties will pave the way for developing a variety of hydrogels with programmable insulin release properties.