Radiation resistance of novel SARS-CoV-2: A Monte Carlo investigation on characterization and determination of gamma-ray attenuation properties

In late December 2019, the new viral pneumonia outbreak was first detected in Wuhan, the largest metropolitan area in China's Hubei province. The 2019–20 coronavirus pandemic is an ongoing pandemic, caused by the severe acute respiratory syndrome-2 (SARS-CoV-2), was named as Coronavirus disease 2019 (COVID-19) by World Health Organization (WHO). It is well known that radiation can cause mutations in bacteria and viruses. Therefore, characterization of the radiation resistance and interaction properties of viruses provides the opportunity in terms of risk assessment and future aspects. In this study, 3 types of viruses (SARS-CoV-CAS Number 587886-51-9, Influenza-CAS Number 141368-69-6 and SARS-CoV-2 GlycoProtein 6VSB.) were modeled with the Monte Carlo simulation method (MCNPX version 2.6.0). The vital radiation attenuation properties such as linear attenuation coefficients, energy absorption buildup factors (EABF), exposure buildup factors (EBF), relative dose distributions (RDD) were examined using advanced simulation methods. Moreover, the spike protein of SARS-CoV-2 is modelled from the structures in the Protein Data Bank. As a result of the study, we could say that the most radiation resistance was observed in SARS-CoV when compared with Influenza and Covid-19. It could be one of the reasons for SARS-CoV’s resistance to mutation from its outbreak time. On the other hand, Covid-19 is more resistant to radiation than Influenza. Therefore it could be expected that Covid-19 would have the similar behaviors against ionizing radiation as Influenza has.


Introduction
In the last twenty years, several viral outbreaks such as "Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) (2002)(2003), H1N1 influenza (2009) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (2012) have been identified in the world [1]. In late December 2019, the new viral pneumonia outbreak was first detected in Wuhan, the largest metropolitan area in China's Hubei province [2]. The 2019-20 coronavirus pandemic is an ongoing pandemic, caused by the severe acute respiratory syndrome-2 (SARS-CoV-2), was named as Coronavirus disease 2019 (COVID-19) by World Health Organization (WHO) [1]. The high mortality is high in older adults 65 years, is unique characteristic of SARS-CoV-2 pandemic [3].
Among these deaths, one of this is quite remarkable because of a newborn death in England. This death is unofficially associated with SARS-CoV-2. People with potential exposure to SARS-CoV-2 were interviewed with a standardised symptom history like cough, fever, kidney failure, pneumonia and severe acute respiratory syndrome both in older adults and people with any age [4]. This approach has been not particularly useful because some infected people have clinically milder or no symptoms that can be linked transmission of the virus on to others. Recently, it has been shown that infection pediatrics with mild symptoms had positivite test results for fecal transmission [5]. Many scientitst believed that those patients whose not in the "detected pool of infected cases", created new "epidemic hotspots" including different materials (plastic, cardboard, metal) during traveling or working [6]. As the resutls of Cov pandemic, most of countries around the world are stepping up efforts to tackle with COVID-19 based on standard recommendations including covering mouth & nose when coughing and sneezing, regular hand washing [5]. The literature review showed that term of ionizing radiation is a considerable tool for virus inactivation aims. The term of radiation is the emission or transmission of energy in the form of waves or particles. It is divided into ionizing and non-ionizing radiation based on its energy and causing of biological effect. The main two characteristics of ionising radiation are high energy levels and high penetration through biological and non-biological materials. Drastic increase in the utilization of ionizing radiation in the field of medicine and industry has been noted over the past years [7,8].
Therefore, ionising radiation is used in food applications, clinical sterilization, and vaccine preparation. Ionising radiation possessed an ability to inactivate viruses and used for vaccine development as it damages the nucleic acids rather than proteins [9]. However, chemical and physical methods can be used for viruses' inactivation, but ionizing radiation has the advantages of penetration throughout the material. On the other hand, the radiation dose can be measured precisely [10,11]. Furthermore, exposure to ionizing radiation has multiple effects on viability and further proliferation of the irradiated cell and damage might occur if the exposure dose exceeded the threshold of each specific tissue. Therefore, fractionation is used to deliver the total radiation dose over fractions to allow intracellular repair [12,13] and the live attenuated microorganisms can be used as vaccine materials [13]. Withal, radiation sensitivity is determined by decimal reduction value (D10) and the shape of the inactivation curve. It is difficult to predict radiation sensitivity but most of the viruses are relatively radiation resistant in a D10 range from 1-10 kGray for gamma photons (Co 60 ) [14]. High energy electron and gamma photons are usually used, and in some cases, x ray and ultraviolet rays are used. However, due to the production of Bremsstrahlung radiation, proteins damage can occur during the process of virus's inactivation using gamma rays [9,15].
It's worth to mention that Gamma radiation is an effective way to inactivate influenza. An exposure of 0.65 kiloGrays (kGy) leads to complete inactivation of the virus, and disruption of protein and haemagglutinating activity occurred at exposure to higher than 200KGy [16,17]. Additionally, the effect on the proteins can be reduced with the use of electron, but electron irradiation is less penetrating than gamma rays [15]. In contrast to high energy electron (>1 MeV), the low energy electron irradiation (LEEI, <500 keV), does not generate x ray radiation and thus, does not require complex shielding [18]. LEEI works efficiently in inactivation of different viruses such as (influenza A (H3N8) and porcine reproductive and respiratory syndrome virus (PRRSV) [18]. On the other hand, ultraviolet radiation demonstrated an efficient role in inactivation of the enveloped MHV coronavirus [19], the enteric human adenovirus (HAdV) reported to be the most UVresistant virus [20]. Evaluation of the virus, radiation, temperatures are crucial factors [21]. The radiation dose used for viral inactivation should be calculated based on the virus concentration, the size, and the temperature of irradiation [22]. Therefore, it is important to assess the use of radiated inactivation and attenuation in virology. On the other hand, direct prediction of virus mutation amounts are significant to understand the evolution of the viruses and to struggle with them [23].
It is well known that radiation can cause mutations in bacteria and viruses. Therefore, charachterization of the radiation resistance and interaction properties of viruses provides the opportunity in terms of of risk assessment and future aspects. However, the literature review showed that no study was performed to investigate the radiation interaction mechanisms of this dose distributions (RDD) were examined using advanced simulation methods. Moreover, the spike protein of SARS-CoV-2 is modelled from the structures in the Protein Data Bank [24]. As it can be seen from the Fig.1, spike protein part is the most external part of viruses. Therefore, it is highly expected to observe the first interactions in spike protein during the interaction between incoming radiation and virus structure. This study aimed to compare gamma ray attenuation properties of GlycoProtein structure of aforementioned virus types. It is well-known that radiation investigations such as dosimetry and radiation detection in micro-scale are difficult or physically impossible. Therefore, advanced simulation techniques and mathematical methods are highly required. Therefore, GlycoProtein structure of viruses sturcture has been modeled in MCNPX (version 2.6.0) Monte Carlo code [25]. We shall discuss simulation details and calculation steps in next sections. The hypohesis of this study is to observe a straight connection between radiation attenuation features and elemental properties of virues structure. In addition, this study aimed to create a new relationship hypothesis between mutation resistance of viruses and radiation attenuation properties for future investigations. In addition, the obtained outcomes from this theoretical study can provide a general idea on radiation attenuation properties of investigated virusues. Moreover, the outcome can also be useful for further investigations on radiation-virus interactions, efforts to improve the harmful effects of viruses.

Viruses
Coronaviruses have five structural proteins in their structures: the Spike (S), Membrane (M), Envelope (E) glycoproteins, Hemagglutinin Esterase (HE) and Nucleocapsid (N) protein (See Figure 1). All viruses have envelope proteins and N protein in their structure but HE is found only in some beta coronaviruses such as SARS-CoV-2 virus. The spike protein of SARS-CoV-2 is modelled from the structures in the Protein Data Bank [24] . The cartoon depiction of the protein is given in Fig. 2 from different viewpoints. (PDB ID: 6VSB) [26] . Mass weight percantage of SARS-CoV-2 is calculated with Materials Studio program and given in Table 1 (with Sedimentation coefficients between 1-10) (Fig. 2), nucleic acids have 1.7 g/ml and overall viruses have 1.35-1.4 g/ml bouyant densities (See Fig.3) [27]. In this study spike protein structure and its atom weight percentages and 1.3 g/ml bouyant density are used in gamma radiation Monte Carlo simulations.

Monte Carlo simulations
In this study, version 2.6.0 of MCNPX [25]

Radiation attenuation properties
In this study, Lambert-Beer's law was used with the help of the following equation to calculate the mass attenuation coefficients ( ) of spine protein structure of investigated viruses [28].
In the formula, ρ denotes the density, t denotes the material thickness and  denotes the mass attenuation coefficient. Units are g/cm 3 , cm and cm 2 /g, respectively. Considering the mixture of elements, the mass attenuation coefficient is calculated by the equation [29] (2).
wheree, wi is a wieght fraction of i th element in the virus structure. With the help of the calculation of the mass attenuation coefficient, which is the key parameter to calculate the attenuation parameters, calculations of MFP values were also calculated (Equation 3). The Mean Free Path (MFP) can be described for both charged particles and photons. It represents the path that a gamma photon takes without interacting with the material and is expressed in terms of linear attenuation coefficient [30].
The term of build-up factor can be defined as the ratio of the amount of radiation at a given location to the amount of radiation coming from this location without interference. The agglomeration factor is defined as the function of the depth of interaction, ie the mean free path.
where Z1 and Z2 are the atomic numbers of the elements corresponding to the ratios of R1 and R2, respectively. R indicates the proportion of glasses studied in a particular energy.
The EBF and EABF values of Hematite doped glasses were estimated for gamma energies up to 15 MeV and for penetration depth up to 40 mfp by using G-P method [31]: where, Moreiver, the G-P fitting parameters (a,b,c,d and Xk) were utilized. These equations contain x as the distance between the source and detector. At 1 mfp, the EBF is coded by b. K(E,X) factor has a meaning of dose multiplication.
Finally, Relative Dose Distribution (RDD) values were determined for investgated viruses. The term of RDD at distance X is calculated using the formula below [32]:

Results and discussions
For  Figure 11 shows that, RDD behaviors of investigated viruses did not changed in different penetration depths (10 mfp, 20 mfp, 30 mfp, 40 mfp). However, slight differences in the lower penetration depths were relatively increased in higher penetration depths.

Conclusion and future aspects
Although many studies have been carried out about the radiation and biological interaction mechanism in the historical process, some issues still remain mysterious. One of these issues is Covid-19 will resist to sunlight's UV radiation. Because a large number of people are expecting that its spread will decline when the weather gets warms up due to sunlight. To clarify this problem, some experiments should be carried out in the lab conditions. The obtained outcomes from this theoretical study has provided a general idea on radiation attenuation properties of investigated virusues. The hypothesis of recent investigation was to observe a direct behavior relationship between spike protein and incoming radiation. The obtained result was approved our hypothesis and slight differences were observed. Of course, this hypothesis should be approved by experimental and clinical investigation in near future.