Structure-Guided Development of Bivalent Aptamers Blocking SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastation to human society through its high virulence, infectivity, and genomic mutations, which reduced the efficacy of vaccines. Here, we report the development of aptamers that effectively interfere with SARS-CoV-2 infection by targeting its spike protein, which plays a pivotal role in host cell entry of the virus through interaction with the viral receptor angiotensin-converting enzyme 2 (ACE2). To develop highly effective aptamers and to understand their mechanism in inhibiting viral infection, we determined the three-dimensional (3D) structures of aptamer/receptor-binding domain (RBD) complexes using cryogenic electron microscopy (cryo-EM). Moreover, we developed bivalent aptamers targeting two distinct regions of the RBD in the spike protein that directly interact with ACE2. One aptamer interferes with the binding of ACE2 by blocking the ACE2-binding site in RBD, and the other aptamer allosterically inhibits ACE2 by binding to a distinct face of RBD. Using the 3D structures of aptamer-RBD complexes, we minimized and optimized these aptamers. By combining the optimized aptamers, we developed a bivalent aptamer that showed a stronger inhibitory effect on virus infection than the component aptamers. This study confirms that the structure-based aptamer-design approach has a high potential in developing antiviral drugs against SARS-CoV-2 and other viruses.

The state of desalination and brine production: A global outlook.

Rising water demands and diminishing water supplies are exacerbating water scarcity in most world regions. Conventional approaches relying on rainfall and river runoff in water scarce areas are no longer sufficient to meet human demands. Unconventional water resources, such as desalinated water, are expected to play a key role in narrowing the water demand-supply gap. Our synthesis of desalination data suggests that there are 15,906 operational desalination plants producing around 95 million m3/day of desalinated water for human use, of which 48% is produced in the Middle East and North Africa region. A major challenge associated with desalination technologies is the production of a typically hypersaline concentrate (termed 'brine') discharge that requires disposal, which is both costly and associated with negative environmental impacts. Our estimates reveal brine production to be around 142 million m3/day, approximately 50% greater than previous quantifications. Brine production in Saudi Arabia, UAE, Kuwait and Qatar accounts for 55% of the total global share. Improved brine management strategies are required to limit the negative environmental impacts and reduce the economic cost of disposal, thereby stimulating further developments in desalination facilities to safeguard water supplies for current and future generations.