Immunization with an inactivated virus is one of the strategies currently being tested towards developing a SARS-CoV-2 vaccine. One of the methods used to inactivate viruses is exposure to high doses of ionizing radiation to damage their nucleic acids. Although gamma-rays effectively induce lesions in the RNA, envelope proteins are also highly damaged in the process. This in turn may alter their antigenic properties, affecting their capacity to induce an adaptive immune response able to confer effective protection. Here, we modelled the impact of sparsely and densely ionizing radiation on SARS-CoV-2 using the Monte Carlo toolkit Geant4-DNA. With a realistic 3D target virus model, we calculated the expected number of lesions in the spike and membrane proteins, as well as in the viral RNA. We show that gamma-rays produce significant spike protein damage, but densely ionizing charged particles induce less membrane damage for the same level of RNA lesions, because a single ion traversal through the nuclear envelope is sufficient to inactivate the virus. We propose that accelerated charged particles produce inactivated viruses with little structural damage to envelope proteins, thereby representing a new and effective tool for developing vaccines against SARS-CoV-2 and other enveloped viruses.
While facial coverings over the nose and mouth reduce the spread of the virus SARS-CoV-2 by filtration, masks capable of viral inactivation by heating could provide a complementary method to limit viral transmission. In this work, we introduce a new virucidal face mask concept based on a reverse-flow reactor driven by the oscillatory flow of human breath. The governing heat and mass transport equation are formulated and solved to analyze designs that evaluate both viral and CO2 transport during inhalation and exhalation. Given limits imposed by the volume and frequency of human breath, the kin…
The wide use of surgical masks has been proven effective for mitigating the spread of respiration diseases, such as COVID-19, alongside social distance control, vaccines, and other efforts. With the newly reported variants, such as Delta and Omicron, a higher spread rate had been found compared to the initial strains. People might get infected even by inhaling fewer loading of viruses. More frequent sterilization of surgical masks is needed to protect the wearers. However, it is challenging to sterilize the commodity surgical masks with a fast and effective method. Herein, we reported the ster…
Contaminated objects or surfaces, referred to as fomites, play a critical role in the spread of viruses, including SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The long persistence of viruses (hours to days) on surfaces calls for an urgent need for surface disinfection strategies to intercept virus transmission and the spread of the disease. Elucidating the physicochemical processes and surface science underlying the adsorption and transfer of virus between surfaces, as well as their inactivation, are important in understanding how the disease is transmitted, and in developing …
The outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a worldwide public health crisis. When the SARS-CoV-2 enters the biological fluids in the human body, different types of biomolecules (in particular proteins) may adsorb on its surface and alter its infection ability. Although great efforts have recently been devoted to the interaction of the specific antibodies with the SARS-CoV-2, it still remains largely unknown how the other serum proteins affect the infection of the SARS-CoV-2. In this work, we systemat…
The spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global health crisis. The binding affinity of SARS-CoV-2 (in particular the receptor binding domain, RBD) to its receptor angiotensin converting enzyme 2 (ACE2) and the antibodies is of great importance in understanding the infectivity of COVID-19 and evaluating the candidate therapeutic for COVID-19. In this work, we propose a new method based on molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) to accurately calculate the free energy of SARS-CoV…
SARS-CoV-2 is a global challenge due to its ability to spread much faster than SARS-CoV, which was attributed to the mutations in the receptor binding domain (RBD). These mutations enhanced the electrostatic interactions. Recently, a new strain was reported in the UK that includes a mutation (N501Y) in the RBD, that possibly increases the infection rate. Using Molecular Dynamics simulations (MD) and Monte Carlo (MC) sampling, we showed that the N501 mutation enhances the electrostatic interactions due to the formation of a strong hydrogen bond between SARS-CoV-2-T500 and ACE2-D355 near the mut…
COVID-19, since emerged in Wuhan, China, has been a major concern due to its high infection rate, leaving more than one million infected people around the world. Huge number of studies tried to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV-1, in order to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV-1 Spike protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the spike proteins …
We propose a novel numerical method able to determine efficiently and effectively the relationship of complementarity between portions of proteins surfaces. This innovative and general procedure, based on the representation of the molecular iso-electron density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, that was unfeasible with previous methods. We first tested the method with a large dataset of known protein complexes obtaining an overall area under the ROC curve of 0.76 in the…
The SARS CoV-2 virus emerged at the end of 2019 and rapidly developed several mutated variants, specifically the Delta and Omicron, which demonstrate higher infectivity and escalating infection cases worldwide. The dominant transmission pathway of this virus is via human-to-human contact and aerosols, but another possible route is through contact with surfaces contaminated with SARS-CoV-2, often exhibiting long-period survival. Here we compare the adsorption capacities of the S1 and S2 subunits of the spike (S) protein from the original variant to that of the S1 subunit from the Delta and Omic…
There is increasing evidence that infection with SARS-CoV-2 can cause a spectrum of neurological symptoms. In this paper, we develop a theoretical concept underlying such neurological COVID-19 consequences by employing a non-equilibrium thermodynamic approach that allows linking the neuronal electric potential with a virus-induced pH variation. Our theoretical findings support further experimental work on therapeutically correcting electrolyte imbalances, such as Na$^+$ and K$^+$, to attenuate the neurological effects of SARS-CoV-2.
Severe Acute Respiratory Syndrome-CoronaVirus 2 (SARS-CoV2) caused the ongoing pandemic. This pandemic devastated the world by killing more than a million people, as of October 2020. It is imperative to understand the transmission dynamics of SARS-CoV2 so that novel and interdisciplinary prevention, diagnostic, and therapeutic techniques could be developed. In this work, we model and analyze the transmission of SARS-CoV2 through the human respiratory tract from a molecular communication perspective. We consider that virus diffusion occurs in the mucus layer so that the shape of the tract does …
The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, as well as antigenic changes that reduce the cross-immunity induced by previous infections or vaccinations. How this functional variation shapes the global evolutionary dynamics has remained unclear. Here we show that selection induced by vaccination impacts on the recent antigenic evolution of SARS-CoV-2; other relevant forces include intrinsic selection and antigenic selection induced by previous infections. We obtain …
The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It infects the cells binding to the angiotensin-converting enzyme 2 receptor (ACE2) which is expressed by cells throughout the airways as targets for cellular entry. Although the majority of persons infected with SARS-CoV-2 experience symptoms of mild upper res…
Nanostructured surfaces enhance ion yields in matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS). The spike protein complex, S1, is one fingerprint signature of Sars-CoV-2 with a mass of 75 kDa. Here, we show that MALDI-MS yields of Sars-CoV-2 spike protein ions in the 100 kDa range are enhanced 50-fold when the matrix-analyte solution is placed on substrates that are coated with a dense forest of multi-walled carbon nanotubes, compared to yields from uncoated substrates. Nanostructured substrates can support the development of mass spectrometry techniques for sensitive p…
The development of highly sensitive and rapid biosensing tools targeted to the highly contagious virus SARS-CoV-2 is critical to tackling the COVID-19 pandemic. Quantum sensors can play an important role, thanks to their superior sensitivity and fast improvements in recent years. Here we propose a molecular transducer designed for nitrogen-vacancy (NV) centers in nanodiamonds, translating the presence of SARS-CoV-2 RNA into an unambiguous magnetic noise signal that can be optically read out. We evaluate the performance of the hybrid sensor, including its sensitivity and false negative rate, an…
In the present study, we have described how by using molecular docking and molecular dynamic (MD) simulation studies the combination drug of ivermectin and doxycycline can be used as a potential inhibitor for SARS-CoV-2 virus. In lieu of unavailability of specific cure of COVID-19 till now various possibilities for individual and combination drugs have been explored by the medical practitioners/scientists for the remedial purpose of CoV-2 infections. $3CL^{pro}$ is the main protease of SARS-CoV-2 virus which plays an essential role in mediating viral replication in the human body. $3CL^{pro}$ …
The virus SARS-CoV-2 has created a situation of global emergency all over the world from the last few months. We are witnessing a helpless situation due to COVID-19 as no vaccine or drug is effective against the disease. In the present study, we have tested the applicability of some combination drugs against COVID-19. We have tried to understand the mechanism of action of some repurposed drugs: Favipiravir (F), Hydroxychloroquine (H) and Oseltamivir (O). The ADME analysis have suggested strong inhibitory possibility of F, H, O combination towards receptor protein of $3CL^{pro}$ of SARS-CoV-2 v…
Protein-protein interaction (PPI) networks have been used to investigate the influence of SARS-CoV-2 viral proteins on the function of human cells, laying out a deeper understanding of COVID--19 and providing ground for drug repurposing strategies. However, our knowledge of (dis)similarities between this one and other viral agents is still very limited. Here we compare the novel coronavirus PPI network against 45 known viruses, from the perspective of statistical physics. Our results show that classic analysis such as percolation is not sensitive to the distinguishing features of viruses, wher…
The SARS-CoV-2 pandemic has added new urgency to the study of viral mechanisms of infection. But while vaccines offer a measure of protection against this specific outbreak, a new era of pandemics has been predicted. In addition to this, COVID-19 has drawn attention to post-viral syndromes and the healthcare burden they entail. It seems integral that knowledge of viral mechanisms is increased through as wide a research field as possible. To this end we propose that quantum biology might offer essential new insights into the problem, especially with regards to the important first step of virus-…
In this manuscript we describe the investigation of the SARS-CoV2 membrane fusion timescale by means of small-angle neutron scattering (SANS) using hydrogen/deuterium contrast variation. After the successful production of virus-like vesicles and human-host-cell-like vesicles we were able to follow the fusion of the respective vesicles in real-time. This was done using deuterated and protonated phospholipids in the vesicles in a neutron-contrast matched solvent. The vesicles were identical apart from either the presence or absence of the SARS-CoV2 spike protein. The human-host-cell-like vesicle…
Breath analysis by ultra-sensitive broadband laser spectroscopy detects SARS-CoV-2 infection
JILA（JILA研究所）；National Institute of Standards and Technology（美国国家标准与技术研究院）；University of Colorado（科罗拉多大学）；University of Basel（巴塞尔大学）；BioFrontiers Institute（生物前沿研究所）；University of Colorado Anschutz Medical Campus（科罗拉多大学安舒茨医学校区）
