Résumé
The COVID-19 pandemic has underscored the need for effective ventilation control in public buildings. This study develops and evaluates a smart ventilation control algorithm (SIREN) that dynamically adjusts zone and system-level HVAC operation to maintain an acceptable COVID-19 infection risk and HVAC energy efficiency. SIREN uses real-time building operation data and Trim & Respond control logic to determine zone primary and system outdoor airflow rates. An EnergyPlus and CONTAM co-simulation framework was developed to assess its performance across various control scenarios and US climate zones. Results show that SIREN can flexibly control infection risk within a customized threshold (e.g. 3%) for every zone, while traditional controls cannot. At the building level, SIREN's HVAC energy consumption is comparable to a fixed 70% outdoor airflow fraction scenario, while its infection risk is lower than the 100% outdoor airflow scenario, illustrating its potential for safe and energy-efficient HVAC operation during pandemics.
Résumé
Over the past 20 years, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2 emerged, causing severe human respiratory diseases throughout the globe. Developing broad-spectrum drugs would be invaluable in responding to new, emerging coronaviruses and to address unmet urgent clinical needs. Main protease (Mpro;also known as 3CL(pro)) has a major role in the coronavirus life cycle and is one of the most important targets for anti-coronavirus agents. We show that a natural product, noncovalent inhibitor, shikonin, is a pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus (HCoV)-HKU1, HCoV-NL63, and HCoV-229E with micromolar half maximal inhibitory concentration (IC50) values. Structures of the main protease of different coronavirus genus, SARS-CoV from the betacoronavirus genus and HCoV-NL63 from the alphacoronavirus genus, were determined by X-ray crystallography and revealed that the inhibitor interacts with key active site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses as well as emerging coronaviruses of the future. Given the importance of the main protease for coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents. IMPORTANCE The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anticoronavirus agents. We solved the crystal structures of the main protease of SARSCoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.
Résumé
The outbreak of COVID-19 has led to worldwide quarantines and telehealth has become the lifeline for patients prone to infection. We propose using a Virtual Reality (VR) system as a playful coping strategy for rehabilitation at home. We hypothesize such a system can improve the physical and mental well-being of the user during play. In this demonstration, we transform the therapy into a playful virtual cat bathing simulation using a VR headset coupled with force feedback gloves. This results in an engaging and feedback-rich scenario where users practice fine motor skills by progressively completing three cat-care tasks.