Dr. S. S. VERMA
The latest novel corona virus has reached pandemic status. While health workers and governments do their part, scientists are trying to understand the virus and develop vaccines and treatments. Corona pandemic has instigated scientists and engineers of all disciplines all over the world to find and develop ways to understand the characteristics of Corona Virus in order to control its spread as well as effect. Physics and physicists along with people from other disciplines like medical, engineering, biosciences are putting all type of efforts in this direction which can help us be better prepared to tackle disease outbreak in the future. When physicists say that there is physics in everything, they mean literally everything, from the generation of virus-laden respiratory droplets to dispersing in the air to inhalation or deposition on surfaces i.e., transmission of corona virus. A team from Johns Hopkins University (USA) has tried to decode the flow physics of corona virus transmission. Scientists say that this can help us be better prepared to tackle disease outbreak in the future. Physicists are also trying to understand to improve the effectiveness of other corona virus preventive measures such as “use of face masks, hand washing, ventilation of indoor environments, and social distancing.”
Fluid mechanics of
The fluid dynamic analyses helped to understand the mechanisms behind how the droplets are generated in the respiratory tract, and also characterize the density, size and velocity of ejected droplets. The team also tried to estimate the settling distance, evaporation time and transport of the particles. They also looked at the effect of external factors such as air currents, temperature and humidity. Previous studies have shown that a single sneeze can generate thousands of droplets, with velocities above 20 metre per second, whereas coughing generates 10-100 times fewer droplets than sneezing with velocities of approximately 10 metre per second. Breathing and talking generate jet velocities less than 5 metre per second. Taking all this into consideration, effective social distancing guideline can be issued. In airborne transmission most of the droplets evaporate within a few seconds to form droplet nuclei – consisting of virions and solid residue – of approximately 10 micrometre in size. These can remain suspended in the air for hours and given the approximately one-hour viability half-life of the virus as these nuclei play an important role in the transmission. The evaporation process and the composition of droplet nuclei require further analysis because these have implications for the viability and potency of the virus that is transported by these nuclei. The final stage of airborne transmission is the inhalation of the virus-laden particles and its deposition in the respiratory mucosa.
Testing corona virus particles against temperature and humidity
One of the biggest unknowns about the corona virus is how changing seasons will affect its spread. The physicists will create individual synthetic corona virus particles without a genome, making the virus incapable of infection or replication. The researchers will test how the structure of the corona virus withstands changes in humidity and temperature, and under what conditions the virus falls apart. The results will help public health officials understand how the virus behaves under various environmental conditions, including in the changing seasons and in microclimates such as air-conditioned offices. This is the application of sophisticated physics instruments and methods to understand how the corona virus will behave as the weather changes.
focusing on COVID-19
Life sciences (medicine and biosciences) professionals are engage in a furious effort to find treatments for the disease and physicists and chemists are a vital and key part of that quest. Though, it is well known that the design engineering as well as working of most of the instruments is based on the basic principles of Physics but still there are some Physics specific instruments which are also finding the applications towards COVID-19 control. Scientists are employing x rays, electrons, and neutrons to decipher and disable the molecular machinery of the novel corona virus. Physics-based tools and methods play an enormous role in understanding structural features and functions of viral particles as well as their effect on the body. Extensive inflammation prevents the lungs from being able to supply enough oxygen to the blood and to remove carbon dioxide. A ventilator is required to forcefully provide sufficient levels of oxygen in blood. A shortage of ventilators remains critical and, in some cases, can be the difference between recovery and death for seriously ill patients. There is a need to come up with the ways to manufacture ventilators quickly, cheaply and reliably. A global team of physicists, engineers and medics have designed a low-cost and simple mechanical ventilator using off-shelf components.
Physics-based techniques play a huge role in the field of structural biology. The vast majority of biological macromolecule structures are obtained by X-ray crystallography. Single biological molecules also diffract X-rays, but only very weakly. Crystallization is helpful because it results in the repetition of huge numbers of molecules in an ordered, 3D lattice, so that all their tiny signals reinforce one another and become detectable – by photographic plates in the early days and by active pixel detectors today. These signals are not images of the molecules, for there are no materials that can substantially refract, and thereby focus, scattered X-rays. Rather, the signals are merely the sum of the contributions of X-rays diffracted from different parts of the molecule. Of course, to obtain the signals in the first place requires X-rays. Nowadays, synchrotron radiation sources – large facilities that accelerate electrons in a continuous ring – are ideal for macromolecular crystallography because they produce high-intensity X-rays with a very narrow spread of wavelengths. At these machines diffraction datasets that would have taken months with X-rays from traditional rotating anode generators take just seconds to? compile.
X-ray crystallography utilizes electro-magnetic radiation to produce wavelengths that can help generate 3D detailed structures of the virus. To help during a pandemic, these techniques have to provide results very quickly. X-ray crystallographic methods used to be slow, but with the use of automation, fast computing platforms and high-quality X-rays, it is possible to get structures very quickly. For structural biologists, x-ray crystallography is by far the most commonly used tool for unraveling protein structures. X-ray crystallography is the fastest method to determine 3D structures and can produce diffraction data in fractions of a second. It also produces the highest-resolution images of structures. The process typically is performed at cryogenic temperatures to limit ionizing-radiation damage to proteins. Small-angle x-ray scattering has dedicated beamlines at each of the synchrotron light sources. The technique lacks the angular resolution of crystallography, but it can be used to examine macromolecules in solution, nearer a protein’s native state at room temperature. The scattering can explore how structures change over time as the virus matures.
Physics instruments like Advanced Photon Source (Argonne National Laboratory, USA), The National Synchrotron Light Source II (Brookhaven National Laboratory, USA), SLAC’s Stanford Synchrotron Radiation Light source (SSRL) (USA), and the Advanced Light Source at Lawrence Berkeley National Laboratory (USA) are operating to keep open several x-ray protein crystallography beam lines strictly for corona virus research. At UK’s Diamond Light Source, scientists are making checks on a novel-corona virus protein crystal sample. Researchers there have focused on the virus’s main protease, a protein that is essential to its replication inside the human host cell. Researchers have used the synchrotron to determine dozens of three-dimensional structures of the main corona virus protease in combination with various ligands that may inhibit the protein’s function and that information could be used in the design of new antiviral drugs. The BESSY II light source in Berlin also resumed operations for corona virus research, which is also ongoing at the Shanghai synchrotron in China, where the first 3D structure of the main protease protein was resolved. Structures of many of the virus’s 28 or 29 proteins (estimates vary on the exact number) have been resolved, both alone and in complexes with various molecules, known as legends that bind to them. Among those resolved structures are the main protease (Mpro), an enzyme that processes long viral polyproteins into shorter functional units; an endoribonuclease called Nsp15; and the spike protein that protrudes from the corona virus surface and initiates infiltration to human cells.
Apart from crystallography, several other techniques are used for protein structure determination. For molecules that resist crystallization, such as large protein complexes, researchers can turn to cryoelectron microscopy (cryo-EM). A team of the University of Texas at Austin (USA) used the technique to determine the structure of the spike protein which is considered as a prime candidate for a vaccine target. However, because the base of the protein is anchored to the hydrophobic viral membrane while the rest of the protein is hydrophilic, the full-length spike protein is hard to crystallize. With the cryo-EM technique, as in x-ray crystallography, myriad individual molecules contribute to a structural determination. Whereas a crystal’s molecules are identically arrayed, the molecules embedded in vitreous ice in cryo-EM are randomly oriented, and their fuzzy, individual 2D projection images are assembled computationally into a single, clear 3D image. Stanford University has kept one of its six cryo-EM instruments at SLAC open for corona virus research and reserved for industrial use. In x-ray crystallography, the photons scatter off the electron charge clouds of the protein molecule’s constituent atoms. As the lightest element, hydrogen scatters x rays extremely weakly. So x-ray crystallographers often must infer the location of hydrogen atoms in the structure, especially in the ionizable amino acids that are often involved in enzyme reactions. In contrast, neutrons interact with atomic nuclei to provide a hydrogen signature comparable to those of the protein’s nitrogen, oxygen, and carbon atoms. Neutron crystallography allows investigators to elucidate the positions of hydrogen atoms, which are invisible to crystallography, in 3D protein structures. That advantage is important because the strongest binding sites on a protein involve hydrogen bonds.
(The author is Professor, Department of Physics SLIET, Longowal)
Dr. S. S. VERMA