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Can common coronavirus compete with novel coronavirus？

Authors:
Zhongneng Xu at Jinan University (Guangzhou, China); the University of Tokyo(Tokyo, Japan)
Zhongneng Xu
  • Jinan University (Guangzhou, China); the University of Tokyo(Tokyo, Japan)
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Abstract

The novel coronavirus found in Wuhan, China caused lethal human respiratory infections, and there is a big problem to control the disease. The application of other viruses to compete with the novel coronavirus was proposed in this paper. On the viewpoint of receptor competition, resource competition, and cross immunity, an attempt should be made to select a natural virus, such as the common coronavirus causing the common cold in human, or transform a virus with biotechnology in order to resist the novel coronavirus. Similar scenarios were suggested to be used to deal with other viruses like human immunodeficiency virus. Microecological communities of viruses could form an independent research area to dig the deeper biological and medical significance. The present study provided the information to further the theoretical implication and medical application of the study of virus interactions.
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1
Can common coronavirus compete with novel coronavirus？ 1
Short title: Coronavirus competition 2
Zhongneng Xu*1, 2 3
4
* --corresponding author, txuzn@jnu.edu.cn ; xuzhongneng@g.ecc.u-tokyo.ac.jp 5
6
1Department of Ecology, Jinan University, Guangzhou 510632, China; 2Department of 7
Aquatic Bioscience, Graduate School of Agricultural and Life Science, the University 8
of Tokyo, Tokyo 113-8657, Japan. 9
2
Abstract 10
The novel coronavirus, SARS-CoV-2, caused lethal human respiratory infections, and 11
there is a big problem to control the disease. The application of other viruses to 12
compete with the novel coronavirus was proposed in this paper. On the viewpoint of 13
receptor competition, resource competition, and cross immunity, an attempt should be 14
made to select a natural virus, such as the common coronavirus causing the common 15
cold in human, or transform a virus with biotechnology in order to resist the novel 16
coronavirus. Similar scenarios were suggested to deal with other viruses like human 17
immunodeficiency virus. Microecological communities of viruses could form an 18
independent research area to dig the deeper biological and medical significance. The 19
present study provided the information to further the theoretical implication and 20
medical application of the study of virus interactions. 21
22
Abstract word count = 131 23
Keywords = SARS-CoV-2, biological competition, virus interaction, viral community
24
3
The novel coronavirus, SARS-CoV-2, caused serious illness [1-3]. Research 25
into preventing and treating the diseases caused by this virus is ongoing. The microbial 26
microecological method, e.g., viral competition, could be considered as one of the 27
proposals. Biological competition between the viruses causing the respiratory tract 28
infections has been reported [4-6]. During the respiratory tract infections, immunity 29
responses to a virus could inhibit the competing viruses, reducing the infections by the 30
later [5-6]. Coronaviruses are also causing pathogens of animal and human respiratory 31
infections [7], and since the novel coronavirus is discovered only recently, its 32
competition with other viruses remains unknown. The theoretical proposal of biological 33
competition between the novel coronavirus and other viruses, as well as the issues of 34
virus community, were herein provided, with the aim to promote experimental studies 35
of the related topics. 36
37
Proposition based on the biological competition to deal with the novel 38
coronavirus 39
Viruses in the human body use resources of cells and are resisted by the 40
immune system; There may be multiple viruses coexisting in the human body, and a 41
complex interspecies relationship between them affects their fates (Figure 1a). Can 42
common coronavirus compete with the novel coronavirus? After a long time of 43
evolution and adaptation, the common coronavirus has adapted well to the 44
environments of the human body. The novel coronavirus has just contacted with 45
humans and should not be well adapted to the human physical environments. If the 46
4
vital organs of the human body are ensured to function normally, the common 47
coronavirus defeating the novel coronavirus in the human body environments is 48
possible. 49
An attempt should be made to select a virus in nature or transform a virus 50
with biotechnology in order to resist the novel coronavirus. If the novel coronavirus 51
belongs to any variants or relatives of human cold viruses, theoretically, to choose the 52
virus or transmute the virus should built on the following conditions. First, the virus that 53
is selected or transformed must have an equal or even stronger infectivity. By doing 54
so, it can compete against the novel coronavirus for the receptors or the other 55
reproductive and survival resources in the human body. Second, virulence of the virus 56
that is selected or transformed must be lower than the novel coronavirus. Third, the 57
competitor can be inhibited by the drugs, or can be controlled by the human immune 58
system under a certain condition. 59
The virus that causes a cold or influenza might satisfy the conditions above 60
and become the competing virus. For example, the common coronavirus, such as 61
human coronavirus OC43 and human coronavirus 229E, are the candidates. To select 62
these viruses are based on the evidence inadequate but worth considering. The 63
common coronavirus and the novel coronavirus belong to the same group and are 64
infectious, but the virulence of them is different in degrees. In that case, to a certain 65
degree, it can be supposed that these two viruses have an equal or similar infecting 66
effect on humans. That is, the molecule groups to infect the humans can be integrated 67
into the same or similar receptor in the human body. And the part that is mutated may 68
5
be the toxophoric groups. Thus, it is probable that the patient is injected with, takes, or 69
inhales a common coronavirus of a thick degree that is enough to have it competing 70
against the novel coronavirus for the human receptor and the other resources in need 71
of the virus growth (Figure 1b). If the common coronavirus defeats the novel 72
coronavirus ultimately, only the common cold is treated in the end. In addition, the 73
symptoms developed by the illness caused by the novel coronavirus like those of 74
respiratory infections developed by the common coronavirus. If the patient is injected 75
into the common coronavirus, then before the novel coronavirus activates the human 76
immunity, the injected virus can pathologically improve on the same or similar immunity 77
to inhabit the further reproduction of the novel coronavirus. Moreover, further 78
investigation and statistics must be done to research the relationship between the 79
novel coronavirus and the cold virus. 80
However, there exist some problems with this proposition in which the cold or 81
influenza virus is used to resist the novel coronavirus. Are those evidences well 82
established to support the biological competition? If the cold or influenza virus is kept 83
in balance with the novel coronavirus, can the artificial conditions help the cold or 84
influenza virus gravitate towards the winning? Is the patient whose physical condition 85
is worsened by the cold or influenza virus more susceptible to the novel coronavirus? 86
For the individual case, is it the cold or influenza virus fatal to the patient? For many 87
cases, can the common cold or influenza virus reproduce under the human immune 88
system or not? Despite of it, the proposition is worth considering, especially before the 89
specific treatment is not found and the novel virus mutates variously and speedily. 90
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91
To deal with other infectious viruses 92
For those viruses that are difficult to deal with such as hepatitis virus and 93
human immunodeficiency virus (HIV), it can also be tried to select a virus in nature or 94
transform a virus with biotechnology to resist the pathogenic virus. Many studies have 95
been done to the pathogenic virus of these infectious diseases whose biological 96
information has been known. Attention must be paid to the mechanism that is related 97
to infecting effects and virulence effects in order to find the treatment. At present, most 98
of the research is based on vaccines of these diseases, the prevention of infecting, the 99
killing of the disease pathogen, etc. Although a dim hope is in sight, much difficulty is 100
still at hand. 101
If the biological competition is taken into consideration to deal with these 102
infectious diseases, except looking for a virus in nature, it is viable to transform a virus 103
by the biotechnological method. Take HIV for instance, the following methods can be 104
used. Scientists can clone nucleic acid sequences which have a relevant infecting 105
effect to HIV, plant them into the neutral virus such as the cold or influenza virus. This 106
new virus, which has the infecting effects of HIV but only the virulence of the cold or 107
influenza virus and thus can be cured by the known drugs, can be made to compete 108
against HIV. In another method, scientists can clone nucleic acid sequences, which 109
contribute to the cure by the known drugs, of some viruses which can be cured by the 110
known drugs and plant them into HIV. This new virus, which has the infecting effects 111
of HIV but can be cured by the known drugs, can be made to compete against HIV. Of 112
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course, scientists can also create a HIV varietas, the living vaccine, which has the 113
infectivity but not severe enough to cause a disease. 114
115
The study on microecological communities of viruses 116
In the case of a new virus infect a person, if other viruses co-exist in the 117
infected person, their interaction, whether synergy or antagonism, might be important 118
to the health of the person. In the condition of antagonism in different viruses in a 119
patient, when the novel coronavirus infects the elderly, adults, and children with the 120
same infection rate, adult people may have the highest mortality rate (especially the 121
mortality rate is standardized by dividing by the mortality rate of the control group which 122
have the same physiological conditions, except for being infected by the novel 123
coronavirus) because adult people's stronger immunity results in lower levels of other 124
viruses before infection, which makes novel coronaviruses less suppressed by other 125
viruses; similarly, a general cold might not be bad news for patients infected by the 126
novel coronavirus, because the microecological balance of viruses might inhibit the 127
novel coronavirus. But when the immune system recognizes the virus, the situation is 128
reversed — adult people's stronger immunity protecting against new viruses more 129
effectively [8]. Thus, the microecological balance of viruses to some extent help 130
immunity system fight new viruses, especially before effective specific immune 131
mechanisms are established. If so, it is paid more attention to use antiviral drugs 132
because antiviral drugs might affect microecological balance of viruses if the antiviral 133
drugs cannot inhibit the novel coronavirus (Figure 1c, 1d, 1e). 134
8
Interactions between viruses within hosts had previously reported, such as 135
the negative correlation between HIV and hepatitis virus [9-10], antagonism of 136
influenza viruses [5-6], cooperation and communication among viruses [11], and 137
evolution of viruses under competition environments [12]. To deeply explore the 138
mechanism insight and medical application of relationship between viruses, the study 139
of ecological communities of viruses could be classified as a special field including 140
several research contents as followed. 141
1) Interaction between viruses in hosts. For an example, competition for 142
resources between viruses is crucial for reproduction and survival. This extends to the 143
competition between physiological mechanisms and biomolecular structures. 144
Moreover, cooperation and mutual benefit between viruses are also possible, including 145
the exchange of genetic material. 146
2) Virus biodiversity in hosts. How to calculate virus biodiversity and the 147
relationship between virus biodiversity and the health of hosts are worth studying. The 148
data of virus biodiversity in the patients during the processes of infection, latent, 149
treatment, and healing has clinical significances. 150
3) The study of beneficial viruses. Not every virus is harmful to the human 151
body. Is there a beneficial virus in an individual? If so, is this benefit based on the 152
production of useful substances to the human body or the maintenance of the 153
ecological balance of the virus to suppress harmful viruses? In addition, do the 154
usefulness and harmfulness of viruses change in different environments? The answers 155
to these questions are helpful to health care and industrial development. 156
9
4) Other scientific issues about communities of viruses. It is believed that with 157
the development of the related techniques, the research contents of virus ecological 158
community will become more and more abundant. For instances, omics researches of 159
the virus community, such as meta-genome and meta-transcriptome, will be analyzed; 160
the exchange of virus species and/or genetic materials of virus between different hosts 161
during contacting processes is also an interesting issue. 162
5) Ethical and legal issues about communities of viruses. Like other biological 163
disciplines, the study of viral communities also requires ethical and legal restrictions. 164
Especially, because the virus research process may bring serious infectious diseases, 165
it is necessary to evaluate the safety risk of related research on virus communities. At 166
the same time, legislation should be adopted to regulate the cultivation of multiple 167
viruses. 168
169
Conclusion 170
Two or more viruses coexisting in the human body may compete for similar 171
resources and trigger similar immune responses. If the common coronavirus (or other 172
low-risk viruses) and the novel coronavirus have such an antagonistic relationship, 173
artificial introduction of the common coronavirus into patients will effectively suppress 174
the novel coronavirus. Similar scenarios will be suggested to deal with other viruses 175
like HIV. Viral competition can be considered as a supplement to existing virus-176
controlling measurements, such as antiviral drugs and immune factors, so the study of 177
this field deserves development. 178
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179
Conflict of Interest 180
The authors declare that they have no conflict of interest. 181
11
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Figures
a
Virus C
(No risk)
Virus A
(High risk)
A
Attacks on Virus
A by
the immune system
×
can’t resist 2 Virus A
Virus B
(Low risk)
B
B
B
B
Attacks on Virus
B by
the immune system
√
The immune
system
can resist 2 Virus B
Resources
Illness
14
×
B
B
B
B
The immune system
can’t resist 6 Virus B
A
×
The immune system
can’t resist 2 Virus A
Heavier illness
√
B
B
B
B
The immune system
can resist 4 Virus B
√
A
can resist 1 Virus A
No illness
b
15
No illness
√
B
B
B
B
The immune system
can resist 2 Virus B
√
B
B
B
B
The immune system
can resist 3 Virus B
No illness
c
16
Illness
A
×
The immune
system
can’t resist 2 Virus A
A
×
can’t resist 3 Virus A
The heaviest illness
d
17
Figure 1 Schematic diagram of virus competition in the patient
It is assumed that all viruses compete for resources and one piece of resource meets
Illness
A
×
can’t resist 2 Virus A
√
B
B
B
B
The immune system
can resist 2 Virus B
A
×
The
immune system
can’t resist 3 Virus A
√
B
B
B
B
The immune system
can resist 3 Virus B
The heaviest illness
e
18
one virus. The immune system can resist at most one virus of Virus A. The immune
system can resist at most 4 viruses of Virus B. Virus C is harmless to the human body
and does not cause immune system reactions. When the number of viruses exceeds
the resistance of the immune system, the person will get sick.
a, Competition of different viruses without treatments — the control
b, Adding the common coronavirus (Virus B)
c, Killing the novel coronavirus (Virus A) by antiviral drugs
d, Killing the common coronavirus (Virus B) by antiviral drugs
e, Killing other competing viruses (Virus C) by antiviral drugs
... 4 Although most of the H-CoVs) cause typically mild respiratory tract infections and the common cold in humans, the nonhuman adapted forms (SARS-CoV, MERS-CoV, SARS-CoV-2) are pathogenic. 5 A high tropism to the respiratory tract cells is observed by SARS-CoV-2, which leads to severe sometimes irreversible lung injury by colonization in these cells and eventually acute respiratory syndrome. ...
... Many members of the coronavirus can survive for 7 to 28 days at the low relative humidity (20%-40%) and dry conditions at room temperature (20 C-21 C). They are also resistant to a wide range of pH changes (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). While, increasing the temperature to 75 C reduces the viral load to ≥5 log 10 in less than 10 minutes. ...
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  • Jun 2017
Author summary Many features of pathogen diversification remain poorly explored although host immunity is recognized as a major driver of pathogen evolution. Influenza A viruses (IAVs) can infect many avian and mammalian hosts, but while few IAV subtypes circulate in human populations, subtype diversity is extensive in wild bird populations. How do these subtypes coexist in wild avian populations and do they compete within these natural host populations? Here we experimentally challenged mallard ducks with different IAVs to study how an initial infection with H3N8 determines the outcome of later infections (duration of infection and virus load) and antibody responses. There was complete protection to re-infection with the same H3N8 virus based on virus isolation. In addition, there was partial protection induced by H3N8 pre-challenge to other subtypes and development of heterosubtypic immunity indicated by significantly shorter infections and reduction in viral load compared to controls. This indicates that subtype dynamics in the host population are not independent. Amongst H3N8 pre-challenged groups, the highest protection was conferred to the H4N5 subtype which was most genetically related to H3N8. The H4N5 challenge also induced an increase in H3 antibody levels in that challenge group and evidence for original antigenic sin or antigenic seniority. Thus, previous infections with IAV can influence the outcome of subsequent challenge with different IAV subtypes. These results not only have relevance to understanding naturally occurring subtype diversity in wild avian populations but also in understanding potential outcomes associated with introduction of novel viruses such as highly pathogenic IAV H5 viruses in wild bird populations.
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Coinfections of the Respiratory Tract: Viral Competition for Resources
Article
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Studies have shown that simultaneous infection of the respiratory tract with at least two viruses is common in hospitalized patients, although it is not clear whether these infections are more or less severe than single virus infections. We use a mathematical model to study the dynamics of viral coinfection of the respiratory tract in an effort to understand the kinetics of these infections. Specifically, we use our model to investigate coinfections of influenza, respiratory syncytial virus, rhinovirus, parainfluenza virus, and human metapneumovirus. Our study shows that during coinfections, one virus can block another simply by being the first to infect the available host cells; there is no need for viral interference through immune response interactions. We use the model to calculate the duration of detectable coinfection and examine how it varies as initial viral dose and time of infection are varied. We find that rhinovirus, the fastest-growing virus, reduces replication of the remaining viruses during a coinfection, while parainfluenza virus, the slowest-growing virus is suppressed in the presence of other viruses.
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Coronaviruses: An Overview of Their Replication and Pathogenesis
Article
Full-text available
  • Feb 2015
Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. Coronaviruses cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease in chickens to potentially lethal human respiratory infections. Here we provide a brief introduction to coronaviruses discussing their replication and pathogenicity, and current prevention and treatment strategies. We also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).
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Pandemic Versus Epidemic Influenza Mortality: A Pattern of Changing Age Distribution
Article
Full-text available
  • Jul 1998
Almost all deaths related to current influenza epidemics occur among the elderly. However, mortality was greatest among the young during the 1918–1919 pandemic. This study compared the age distribution of influenza-related deaths in the United States during this century's three influenza A pandemics with that of the following epidemics. Half of influenza-related deaths during the 1968–1969 influenza A (H3N2) pandemic and large proportions of influenza-related deaths during the 1957–1958 influenza A (H2N2) and the 1918–1919 influenza A (H1N1) pandemics occurred among persons < 65 years old. However, this group accounted for decrementally smaller proportions of deaths during the first decade following each pandemic. A model suggested that this mortality pattern may be explained by selective acquisition of protection against fatal illness among younger persons. The large proportion of influenza-related deaths during each pandemic and the following decade among persons < 65 years old should be considered in planning for pandemics.
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The Evolution of Virulence in RNA Viruses under a Competition-Colonization Trade-Off
Article
  • Nov 2010
  • B MATH BIOL
RNA viruses exist in large intra-host populations which display great genotypic and phenotypic diversity. We analyze a model of viral competition between two different viral strains infecting a constantly replenished cell pool, in which we assume a trade-off between the virus' colonization skills (cell killing ability or virulence) and its local competition skills (replication performance within coinfected cells). We characterize the conditions that allow for viral spread by means of the basic reproductive number and show that a local coexistence equilibrium exists, which is asymptotically stable. At this equilibrium, the less virulent competitor has a reproductive advantage over the more virulent colonizer. The equilibria at which one strain outcompetes the other one are unstable, i.e., a second viral strain is always able to permanently invade. One generalization of the model is to consider multiple viral strains, each one displaying a different virulence. However, to account for the large phenotypic diversity in viral populations, we consider a continuous spectrum of virulences and present a continuum limit of this multiple viral strains model that describes the time evolution of an initial continuous distribution of virulence. We provide a proof of the existence of solutions of the model's equations and present numerical approximations of solutions for different initial distributions. Our simulations suggest that initial continuous distributions of virulence evolve towards a stationary distribution that is extremely skewed in favor of competitors. Consequently, collective virulence attenuation takes place. This finding may contribute to understanding the phenomenon of virulence attenuation, which has been reported in previous experimental studies.
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